A Safety, Tolerability, Pharmacokinetics/Pharmacodynamics Study of HEC169584 Capsules in Healthy Subjects

Official title

A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of Single and Multiple Doses of HEC169584 Capsules and the Effect of Food on Its Pharmacokinetics in Healthy Subjects

Overview

The safety, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) characteristics study of HEC169584 capsules in healthy subjects .

Detailed description

This trial adopts a single - center, randomized, double - blind, placebo - controlled, dose - escalation trial design.

This trial is divided into two parts. The first part consists of a single - ascending - dose (SAD) trial and a food - effect (FE) trial. The second part is a multiple - ascending - dose (MAD) tria.

Screening will be conducted within 28 days prior to the first drug administration. After all test results are obtained, inclusion and exclusion criteria will be verified. Eligible subjects will be admitted to the research center one day before drug administration (D - 1). Researchers will assign random numbers to eligible subjects of the same dose group in ascending order according to their screening numbers, and conduct relevant examinations and collect blood, urine, and fecal samples (if necessary) at the time points specified in the protocol.

Interventions

• Drug HEC169584 capsule
  Each dose of HEC83518 will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.
• Drug placebo
  The placebo will be administered with approximately 240 mL of water in the morning after fasting for at least 10 hours overnight.

Primary outcome measures

• Adverse event [Time frame: up to 27 days]

Secondary outcome measures (12)

• PK parameters - AUC0-∞ [Time frame: up to 48 hours]
• PK parameters - AUC0-t [Time frame: up to 48 hours]
• PK parameters - Cmax [Time frame: up to 48 hours]
• PK parameters - tmax [Time frame: up to 48 hours]
• PK parameters - t½ [Time frame: up to 48 hours]
• PK parameters -Vz/F [Time frame: up to 48 hours]
• PK parameters -MRT [Time frame: up to 48 hours]
• PK parameters -CL/F [Time frame: up to 48 hours]
• PK parameters -The Accumulation Ratio(R) [Time frame: up to 15 days]
• PK parameters -Food Effect on the Cmax [Time frame: up to 48 hours]
• PK parameters -Food Effect on the AUC [Time frame: up to 48 hours]
• The pharmacodynamics of HEC169584 capsules [Time frame: Time Frame: up to 28 days]

Eligibility criteria

Inclusion criteria

• Subjects should understand and abide by the research procedures, volunteer to participate, and sign the informed consent form.
• When signing the informed consent form, subjects should be between 18 and 45 years old (including the boundary values), and both genders are eligible.
• Male subjects should weigh ≥ 50.0 kg, and female subjects should weigh ≥ 45.0 kg. For the single - dose trial, the body mass index \[BMI = weight (kg) / height² (m²)\] should be within the range of 18.0 - 28.0 kg/m² (including the boundary values). For the multiple - dose trial, the BMI should be within the range of 18.0 - 30.0 kg/m² (including the boundary values).
• Subjects enrolled in the MAD (Multiple - Ascending - Dose) trial should also meet the requirement that 2.6 mmol/L (100 mg/dL) ≤ LDL - C < 4.1 mmol/L (160 mg/dL).
• The results of vital signs, physical examinations, clinical laboratory tests, electrocardiograms, chest X - rays (posteroanterior view), abdominal color Doppler ultrasounds, etc. should be normal, or if judged as abnormal by the investigator, they should be of no clinical significance.
• Subjects (including their partners) should voluntarily adopt effective contraceptive measures from the screening stage until 3 months after the last drug administration, and should have no plans for sperm or egg donation.

Exclusion criteria

• Subjects had clinically significant diseases as follows (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, neoplastic, pulmonary, immunological, mental, or cardiovascular and cerebrovascular diseases) before screening.
• Subjects with allergic constitution (allergic to multiple drugs or foods).
• Subjects who smoked more than 5 cigarettes per day on average within 3 months before screening, or smoked within 48 hours before taking the investigational product, or could not stop using any tobacco products during the trial.
• Subjects had a history of dysphagia before screening, or had a history of gastrointestinal, hepatic, or renal diseases or surgeries that potentially affect the absorption, distribution, metabolism, and excretion of the investigational product (except uncomplicated appendectomy and hernia repair).
• Subjects had a history of alcoholism within 1 year before screening (consuming 14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine), or had a positive alcohol breath test during the screening period.
• Subjects had a history of drug abuse or used drugs within 2 years before screening, or had a positive urine drug screening during the screening period.
• Subjects donated blood or lost blood ≥ 400 mL within 3 months before screening, or planned to donate blood within 1 month after the end of the trial.
• Subjects had a history of thyroid diseases, or the thyroid - stimulating hormone (TSH) index in the thyroid function test during the screening period was beyond the normal range.
• Subjects had a corrected QT interval (QTcF = QT/RR0.33 calculated by the Fridericia formula) of the 12 - lead electrocardiogram > 450 ms during screening.
• Subjects had a glomerular filtration rate < 90 mL/min (the glomerular filtration rate is calculated using the simplified MDRD formula: for men, eGFR = 186 × creatinine (mg/dL)-1.154 × age - 0.203; for women, eGFR = 186 × creatinine (mg/dL)-1.154 × age - 0.203 × 0.742). Note: The unit of creatinine in the formula is mg/dL. When calculating, the creatinine result in μmol/L needs to be converted to mg/dL, and 1 μmol/L = 0.01131 mg/dL.
• Subjects received vaccination within 1 month before screening, or planned to receive vaccination during the trial.
• Subjects took inhibitors and/or inducers of CYP3A4, CYP2C8, P - gp, or BCRP within 4 weeks before screening.
• Subjects took any prescription drugs, over - the - counter drugs, any vitamin products, or Chinese herbal medicines within 14 days before screening.
• Subjects consumed foods or beverages containing chocolate, caffeine, xanthine, alcohol, or grapefruit within 48 hours before the first drug administration.
• Subjects developed an acute illness or had concomitant medications from the screening stage to before the first drug administration.
• Subjects had a history of fainting at the sight of needles or blood, could not tolerate intravenous puncture for blood collection, or had difficulty in blood collection.
• Lactating or pregnant women, or women of child - bearing potential with a positive pregnancy test.
• Subjects participated in other clinical trials within 3 months before screening (if the subject withdrew from the study before treatment, that is, was not randomized or did not receive treatment, they can be enrolled in this study).
• Subjects tested positive for any one of hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or treponema pallidum antibody.
• Subjects had special dietary requirements and could not accept the unified diet.
• Subjects with other factors that, in the investigator's opinion, make them inappropriate to participate in this trial.

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

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• No. 49, Huayuan North Road, Haidian District, Beijing Municipality — Beijing

Identifiers

NCT: NCT07099118 · HEC169584-NASH-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗