A Drug-Drug Interaction Study Between NTQ5082 Capsules and Midazolam Oral Solutio
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 18
- 主要终点
- Maximum Plasma Concentration (Cmax) of Midazolam
研究概览
简要总结
This is a single-center, non-randomized, open-label, single-sequence, self-controlled drug-drug interaction study in healthy participants.
The main purpose of the study is to evaluate whether a single dose and repeated daily doses of NTQ5082 capsules affect the pharmacokinetics of midazolam oral solution. Midazolam is used in this study as a probe drug to assess the activity of cytochrome P450 3A (CYP3A), an enzyme involved in the metabolism of many medicines.
Approximately 18 healthy male and female participants will be enrolled. Participants will receive a single oral dose of midazolam 2 mg on Days 1, 4, and 11. NTQ5082 200 mg will be administered orally once daily from Day 4 through Day 12. Blood samples will be collected to measure the concentrations of midazolam and its metabolite, 1'-hydroxymidazolam, and to calculate pharmacokinetic parameters.
The safety and tolerability of midazolam administered alone and together with NTQ5082 will also be evaluated through adverse event monitoring, laboratory tests, vital signs, physical examinations, and electrocardiograms. The study includes a screening and protocol-required vaccination period, an inpatient treatment period, and a safety follow-up telephone call within 7 days after discharge.
详细描述
This is a single-center, non-randomized, open-label, single-sequence, self-controlled drug-drug interaction study designed to evaluate the effect of single and multiple oral doses of NTQ5082 capsules on the pharmacokinetics of midazolam oral solution, a CYP3A probe substrate, in healthy participants. The study will also evaluate the safety and tolerability of the concomitant administration of NTQ5082 and midazolam.
Approximately 18 healthy male and female participants are planned to be enrolled. The study consists of a screening and protocol-required vaccination period from Day -28 to Day -1, an inpatient study period from Day 1 to Day 13, and a safety follow-up period within 7 days after discharge.
Participants will provide written informed consent between Day -28 and Day -14. After preliminary screening, eligible participants will receive the protocol-required vaccination between Day -28 and Day -14. Additional screening assessments and confirmation of eligibility will be conducted between Day -7 and Day -1. Screening assessments will include demographic information, medical history, medication history, previous clinical trial participation, vital signs, physical examination, electrocardiography, and laboratory tests.
Eligible participants will be admitted to the clinical research center on Day -1 and will remain in the center through Day 12. A discharge assessment will be performed on Day 13 or at the time of early withdrawal.
Participants will receive midazolam oral solution 2 mg (1 mL) as a single oral dose under fasting conditions on Days 1, 4, and 11. Participants will also receive NTQ5082 capsules 200 mg, administered as two 100 mg capsules, once daily under fasting conditions from Day 4 through Day 12.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 aged 18 to 45 years, inclusive.
- •Body mass index (BMI) from 19.0 to 26.0 kg/m², inclusive, with a body weight of at least 50 kg for males and at least 45 kg for females.
- •Participants who voluntarily sign the informed consent form before any study-related procedure and fully understand the study content, procedures, and potential adverse reactions.
- •Participants who are able to communicate effectively with the investigator and understand and comply with all study requirements.
- •Participants who are willing to receive an ACYW135 meningococcal vaccine and a pneumococcal vaccine at least 14 days before the first dose. Repeat vaccination is not required if the participant received a pneumococcal vaccine within 5 years before dosing or an ACYW135 meningococcal vaccine within 3 years before dosing.
排除标准
- •Participation in any other drug clinical trial and receipt of an investigational medicinal product within 3 months before admission to the clinical research unit.
- •A history of chronic or active gastrointestinal disease within 3 years before admission, including esophageal disease, gastritis, gastric ulcer, gastroesophageal reflux disease, enteritis, active gastrointestinal bleeding, or gastrointestinal surgery, that is considered clinically significant by the investigator.
- •A confirmed disease of the central nervous, cardiovascular, gastrointestinal, respiratory, endocrine, urinary, hematologic and lymphatic, or metabolic system requiring medical intervention, or any other condition, including a psychiatric history, that may make the participant unsuitable for the study.
- •A known or suspected history of immunodeficiency, such as frequent recurrent infections, or a history of hereditary or acquired complement deficiency.
- •A confirmed history of infection caused by encapsulated microorganisms within 6 months before admission, including but not limited to Streptococcus pneumoniae, Bacillus anthracis, Salmonella species, Salmonella Typhi, Klebsiella pneumoniae, Pseudomonas aeruginosa, Bacteroides fragilis, Neisseria meningitidis, Haemophilus influenzae, or Legionella pneumophila.
- •A history of tuberculosis infection or current tuberculosis infection.
- •An active systemic bacterial, viral, or fungal infection within 14 days before the first dose.
- •Symptoms such as dizziness, headache, abdominal pain, diarrhea, or constipation within 14 days before the first dose that, in the investigator's opinion, make the participant unsuitable for the study.
- •Known hypersensitivity to either study intervention, any of their components, or related preparations, or a history of allergy to drugs, food, or other substances.
- •Inability to tolerate venipuncture or a history of fainting in response to blood or needles.
- •Surgery within 6 months before admission that, in the investigator's opinion, may affect drug absorption, distribution, metabolism, or excretion; any surgical procedure within 30 days before admission; or planned surgery during the study.
- •Use of any medication within 28 days before admission, including prescription drugs, nonprescription drugs, traditional Chinese medicines, Chinese patent medicines, or dietary supplements, or use within 5 half-lives of the medication at screening, whichever period is longer.
- •Receipt of any vaccine, including a live attenuated vaccine, within 14 days before the first dose, except for the meningococcal and pneumococcal vaccines required by the protocol, or planned vaccination during the study.
- •Corrected QT interval (QTc) of at least 450 milliseconds for males or at least 460 milliseconds for females at screening.
- •Blood donation or significant blood loss of more than 400 mL, blood transfusion, or receipt of blood products within 3 months before admission, or an intention to donate blood or blood components during the study or within 3 months after study completion.
- •A history of drug abuse or use of soft drugs, such as marijuana, or hard drugs, such as cocaine or phencyclidine, within 1 year before admission.
- •Regular smoking or smoking more than 5 cigarettes per day within 3 months before admission, or inability to discontinue all tobacco products during the study.
- •Alcohol abuse or regular alcohol consumption within 6 months before admission, defined as more than 14 units of alcohol per week, where 1 unit is equivalent to 360 mL of beer, 45 mL of 40% spirits, or 150 mL of wine, or unwillingness to abstain from alcohol and alcohol-containing products during the study.
- •Consumption of excessive amounts of tea, coffee, or other caffeinated beverages, defined as more than 8 cups per day, with 1 cup equal to 250 mL, or unwillingness to discontinue such beverages during the study.
- •Consumption within 7 days before admission of grapefruit, grapefruit-containing products, or other foods that may affect drug absorption, distribution, metabolism, or excretion, or unwillingness to avoid such foods during the study.
- •Special dietary requirements or inability to comply with the standardized diet provided during the study.
- •Female participants who are pregnant or breastfeeding; who have had unprotected sexual intercourse within 14 days before admission; who have used oral contraceptives within 30 days before admission; or who have used long-acting estrogen or progestogen injections or implants within 6 months before admission.
- •Participants, or their partners, who plan pregnancy or sperm or oocyte donation from the time of signing informed consent through 3 months after the last dose, or who are unwilling to use at least one nonpharmacologic contraceptive method, such as complete abstinence, an intrauterine device, or partner sterilization.
- •Clinically significant abnormalities, as determined by the investigator, in physical examination, electrocardiogram, abdominal ultrasound, chest radiograph, vital signs, or laboratory examinations, including hematology, urinalysis, blood chemistry, procalcitonin, coagulation, thyroid function, infectious disease screening, or serum pregnancy testing for females.
- •A positive alcohol breath test or drug abuse screening result.
- •Any other condition that, in the investigator's opinion, may prevent the participant from completing the study or otherwise make the participant unsuitable for participation.
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of Midazolam
时间窗: Predose through 48 hours postdose on Days 1, 4, and 11
The maximum observed plasma concentration (Cmax) of midazolam will be determined from the plasma concentration-time data following a single oral dose of midazolam 2 mg administered alone on Day 1, coadministered with the first dose of NTQ5082 200 mg on Day 4, and coadministered with NTQ5082 200 mg after repeated NTQ5082 dosing on Day 11.
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Midazolam
时间窗: Predose through 48 hours postdose on Days 1, 4, and 11
The area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) of midazolam will be calculated after midazolam administration alone on Day 1, with the first dose of NTQ5082 on Day 4, and after repeated NTQ5082 dosing on Day 11.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Midazolam
时间窗: Predose through 48 hours postdose on Days 1, 4, and 11
The area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of midazolam will be calculated after midazolam administration alone on Day 1, with the first dose of NTQ5082 on Day 4, and after repeated NTQ5082 dosing on Day 11.
次要结局
- Time to Maximum Plasma Concentration (Tmax) of Midazolam(Predose through 48 hours postdose on Days 1, 4, and 11)
- Terminal Elimination Half-Life (t1/2z) of Midazolam(Predose through 48 hours postdose on Days 1, 4, and 11)
- Apparent Oral Clearance (CLz/F) of Midazolam(Predose through 48 hours postdose on Days 1, 4, and 11)
- Number of Participants With Treatment-Emergent Adverse Events(From the first dose on Day 1 through the safety follow-up conducted within 7 days after discharge, approximately through Day 20)
研究者
Guoping Yang
Professor of Clinical Pharmacology
The Third Xiangya Hospital of Central South University