Food Effect and Multiple-Dose Study of Chiglitazar/Metformin Extended-Release Tablets

Official title

A Phase I Clinical Study to Assess the Food Effect and Multiple Dose Pharmacokinetic of Chiglitazar/Metformin Extended-Release Fixed Dose Combination Tablets

Overview

This trial includes two parts: a food effect (FE) study and a multiple-dose pharmacokinetic (PK) study. The FE study is a randomized, open-label, two-period, two-sequence crossover study designed to evaluate the effect of a high-fat meal on the PK of a single oral dose of Chiglitazar/Metformin extended-release tablets in healthy adult Chinese participants. The multiple-dose PK study is an open-label study designed to evaluate the PK characteristics of Chiglitazar/Metformin extended-release tablets in healthy adult Chinese participants following multiple oral doses.

Interventions

• Drug Chiglitazar/Metformin extended-release tablets under fasting conditions
  a single dose of Chiglitazar/Metformin extended-release tablets under fasting conditions
• Drug Chiglitazar/Metformin extended-release tablets after a high-fat meal
  a single dose of Chiglitazar/Metformin extended-release tablets after a high-fat meal
• Drug multiple-dose of Chiglitazar/Metformin extended-release tablets
  a single dose on Day 1, once-daily consecutive doses from Day 4 to Day 10

Primary outcome measures

• FE Study: Maximum plasma concentration (Cmax) [Time frame: Pre-dose and at multiple timepoints post-dose up to 72 hours]
• FE Study: Area Under the Plasma Concentration-Time Curve (AUC) [Time frame: Pre-dose and at multiple timepoints post-dose up to 72 hours]
• FE Study: Time to Maximum Plasma Concentration（Tmax） [Time frame: Pre-dose and at multiple timepoints post-dose up to 72 hours]
• FE Study: Elimination Half-life （t1/2） [Time frame: Pre-dose and at multiple timepoints post-dose up to 72 hours]
• FE Study: Apparent Total Clearance （CL/F） [Time frame: Pre-dose and at multiple timepoints post-dose up to 72 hours]
• FE Study: Apparent Volume of Distribution during the terminal phase （Vz/F） [Time frame: Pre-dose and at multiple timepoints post-dose up to 72 hours]
• Multiple-dose PK study: Maximum plasma concentration (Cmax) [Time frame: predose to 72 hours after the last dose (7 consecutive days of dosing)]
• Multiple-dose PK Study: Area Under the Plasma Concentration-Time Curve (AUC) [Time frame: predose to 72 hours after the last dose (7 consecutive days of dosing)]
• Multiple-dose PK Study: Time to Maximum Plasma Concentration（Tmax） [Time frame: predose to 72 hours after the last dose (7 consecutive days of dosing)]
• Multiple-dose PK Study: steady-state peak concentration (Cmax,ss) [Time frame: predose to 72 hours after the last dose (7 consecutive days of dosing)]

Secondary outcome measures (4)

• Incidence of Adverse Events (AEs) [Time frame: up to Day 16]
• Change from baseline in hematology parameters: white blood cell count, neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count, red blood cell count , hemoglobin, hematocrit, platelet count [Time frame: up to Day 13]
• Changes from baseline in serum chemistry parameters [Time frame: up to Day 13]
• Changes from baseline in urinalysis parameters: urine protein, urine ketones, urine glucose, urine pH, urine leukocytes, urine red blood cells [Time frame: up to Day 13]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07511010 · CGZ111

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗