Bioequivalence Study of Chiglitazar/Metformin Extended-Release Fixed Dose Combination Tablets in Healthy Subjects: A Randomized, Open-Label, Two-Period, Single-dose, Crossover Trial Under Fed Conditions
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 64
- 主要终点
- Maximum plasma concentration (Cmax)
研究概览
简要总结
This is a single-center, randomized, open-label, two-period, two-sequence crossover bioequivalence study under fed conditions. The primary objective is to evaluate the bioequivalence of a single oral dose of the test formulation compared with the reference formulation in the fed state.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female participants；
- •Age from 18 to 45 years, inclusive；
- •Body Mass Index (BMI) between 19.0 and 26.0 kg/m² (inclusive). Male participants must weigh at least 50.0 kg, and female participants must weigh at least 45.0 kg；
- •From the time of signing the informed consent form until 3 months after the last dose, participants must have no plans for pregnancy or sperm donation and must be willing to use effective contraceptive measures；
- •Voluntarily agrees to participate in the study and signs the informed consent form.
排除标准
- •Any clinically significant abnormalities in laboratory tests or a history of clinically significant diseases, including but not limited to cardiovascular, cerebrovascular, hepatic, renal, respiratory, gastrointestinal, neurological, hematological, immune, oncological, psychiatric, or endocrine/metabolic disorders;
- •Known history of severe allergies (e.g., allergy to more than 3 allergens, allergies affecting the lower respiratory tract such as allergic asthma, allergies requiring glucocorticoid treatment) or a known history of allergy to any component of the investigational products;
- •Previous surgery that could affect drug absorption, distribution, metabolism, or excretion (e.g., subtotal gastrectomy), or a history of gastrointestinal, hepatic, or renal disease within the last 6 months that could affect drug absorption or metabolism;
- •Surgery within 3 months prior to screening or planned surgery during the study period;
- •Received any vaccination within 1 month prior to screening or plan to receive any vaccination during the study period;
- •History of infectious disease treated with significant use of antibiotics within 3 months before the first dose, or any infectious disease within 7 days before the first dose;
- •Presence of gastrointestinal symptoms (e.g., diarrhea, constipation, nausea, vomiting) within 7 days before the first dose, which the investigator deems unsuitable for study participation;
- •Use of any prescription drugs, over-the-counter drugs, or Chinese herbal medicines within 1 month before the first dose; or use of vitamin products within 2 weeks before enrollment;
- •History of drug or substance abuse, or a positive alcohol or urine drug screening test;
- •Intolerance to venipuncture, or a history of fainting in response to needles or blood;
- •Fasting blood glucose > 6.1 mmol/L or < 3.9 mmol/L at screening, and/or a history of hypoglycemia/syncope;
- •Participation in any interventional clinical trial within 3 months prior to screening;
- •Blood donation or significant blood loss (> 200 mL) within 3 months prior to screening;
- •Pregnant or lactating women;
- •Weekly alcohol consumption of more than 14 units within 3 months prior to screening, consumption of alcohol within 48 hours before the first dose, or inability to abstain from alcohol during the study;
- •Smokes more than 5 cigarettes per day within 3 months prior to screening, has smoked within 48 hours before the first dose, or is unable to abstain from smoking during the study;
- •Excessive daily consumption of tea, coffee, and/or caffeinated beverages within 3 months prior to screening, or consumption of such beverages within 48 hours before the first dose;
- •Consumption of grapefruit or grapefruit-related citrus fruits (e.g., Seville oranges, pomelos), star fruit, papaya, pomegranate, or their products within 14 days before the first dose;
- •Glomerular Filtration Rate (GFR) < 90 mL/min/1.73 m²;
- •Systolic blood pressure < 90 mmHg or ≥ 140 mmHg, or diastolic blood pressure < 50 mmHg or ≥ 90 mmHg at screening;
- •A positive test result at screening for any of the following: Human Immunodeficiency Virus antibody, Treponema pallidum antibody, Hepatitis B surface antigen, or Hepatitis C virus antibody;
- •Inability to comply with the standardized diet (e.g., intolerance to the high-fat meal, lactose intolerance) or has difficulty swallowing;
- •Plans to or is required to engage in strenuous physical activity or exercise during the study period;
- •Any other condition that, in the opinion of the investigator, makes the participant unsuitable for inclusion in the study.
研究组 & 干预措施
Sequence T-R (dose 1)
Participants will receive Chiglitazar/Metformin extended-release fixed dose combination tablets at dose level 1 in Period 1 on Day 1, followed by Chiglitazar tablets and Metformin extended-release tablets at dose level 1 in Period 2 on Day 1.
干预措施: Chiglitazar/Metformin extended-release fixed-dose combination tablet, dose 1 (Drug)
Sequence T-R (dose 1)
Participants will receive Chiglitazar/Metformin extended-release fixed dose combination tablets at dose level 1 in Period 1 on Day 1, followed by Chiglitazar tablets and Metformin extended-release tablets at dose level 1 in Period 2 on Day 1.
干预措施: Chiglitazar tablet, dose 1 (Drug)
Sequence T-R (dose 1)
Participants will receive Chiglitazar/Metformin extended-release fixed dose combination tablets at dose level 1 in Period 1 on Day 1, followed by Chiglitazar tablets and Metformin extended-release tablets at dose level 1 in Period 2 on Day 1.
干预措施: Metformin extended-release tablet, dose 1 (Drug)
Sequence R-T (dose 1)
Participants receive chiglitazar tablet and metformin extended-release tablet at dose level 1 in Period 1 on Day 1, followed by chiglitazar/metformin extended-release fixed-dose combination tablet at dose level 1 in Period 2 on Day 1.
干预措施: Chiglitazar/Metformin extended-release fixed-dose combination tablet, dose 1 (Drug)
Sequence R-T (dose 1)
Participants receive chiglitazar tablet and metformin extended-release tablet at dose level 1 in Period 1 on Day 1, followed by chiglitazar/metformin extended-release fixed-dose combination tablet at dose level 1 in Period 2 on Day 1.
干预措施: Chiglitazar tablet, dose 1 (Drug)
Sequence R-T (dose 1)
Participants receive chiglitazar tablet and metformin extended-release tablet at dose level 1 in Period 1 on Day 1, followed by chiglitazar/metformin extended-release fixed-dose combination tablet at dose level 1 in Period 2 on Day 1.
干预措施: Metformin extended-release tablet, dose 1 (Drug)
Sequence T-R (dose 2)
Participants receive chiglitazar/metformin extended-release fixed-dose combination tablet at dose level 2 in Period 1 on Day 1, followed by chiglitazar tablet and metformin extended-release tablet at dose level 2 in Period 2 on Day 1.
干预措施: Chiglitazar/Metformin extended-release fixed-dose combination tablet, dose 2 (Drug)
Sequence T-R (dose 2)
Participants receive chiglitazar/metformin extended-release fixed-dose combination tablet at dose level 2 in Period 1 on Day 1, followed by chiglitazar tablet and metformin extended-release tablet at dose level 2 in Period 2 on Day 1.
干预措施: Chiglitazar tablet, dose 2 (Drug)
Sequence T-R (dose 2)
Participants receive chiglitazar/metformin extended-release fixed-dose combination tablet at dose level 2 in Period 1 on Day 1, followed by chiglitazar tablet and metformin extended-release tablet at dose level 2 in Period 2 on Day 1.
干预措施: Metformin extended-release tablet, dose 2 (Drug)
Sequence R-T (dose 2)
Participants receive chiglitazar tablet and metformin extended-release tablet at dose level 2 in Period 1 on Day 1, followed by chiglitazar/metformin extended-release fixed-dose combination tablet at dose level 2 in Period 2 on Day 1.
干预措施: Chiglitazar/Metformin extended-release fixed-dose combination tablet, dose 2 (Drug)
Sequence R-T (dose 2)
Participants receive chiglitazar tablet and metformin extended-release tablet at dose level 2 in Period 1 on Day 1, followed by chiglitazar/metformin extended-release fixed-dose combination tablet at dose level 2 in Period 2 on Day 1.
干预措施: Chiglitazar tablet, dose 2 (Drug)
Sequence R-T (dose 2)
Participants receive chiglitazar tablet and metformin extended-release tablet at dose level 2 in Period 1 on Day 1, followed by chiglitazar/metformin extended-release fixed-dose combination tablet at dose level 2 in Period 2 on Day 1.
干预措施: Metformin extended-release tablet, dose 2 (Drug)
结局指标
主要结局
Maximum plasma concentration (Cmax)
时间窗: Pre-dose and at multiple timepoints post-dose up to 72 hours
Area Under the Plasma Concentration-Time Curve from time zero to the last measurable concentration (AUC0-last)
时间窗: Pre-dose and at multiple timepoints post-dose up to 72 hours
Area Under the Plasma Concentration-Time Curve from time zero to infinity (AUC0-∞)
时间窗: Pre-dose and at multiple timepoints post-dose up to 72 hours
次要结局
- Incidence of Adverse Events (AEs)(up to Day 11)
- Apparent Total Clearance （CL/F）(Pre-dose and at multiple timepoints post-dose up to 72 hours)
- Apparent Volume of Distribution during the terminal phase （Vz/F）(Pre-dose and at multiple timepoints post-dose up to 72 hours)
- Time to Maximum Plasma Concentration（Tmax）(Pre-dose and at multiple timepoints post-dose up to 72 hours)
- Elimination Half-life （t1/2）(Pre-dose and at multiple timepoints post-dose up to 72 hours)