A Phase 1 Study to Evaluate the Effect of Rifampin on the Pharmacokinetics of MDR-001 and the Effect of Itraconazole on the Pharmacokinetics of MDR-001 in Healthy Adult Study Participants
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Cmax of MDR-001
研究概览
简要总结
A Phase I, open-label, fixed-sequence, two-part drug-drug interaction study in healthy Chinese adults to evaluate the effect of multiple-dose rifampin (Part A) or itraconazole (Part B) on the single-dose pharmacokinetics of MDR-001, an oral GLP-1 receptor agonist.
详细描述
This phase 1, single-center, open-label, fixed-sequence drug-drug interaction study will evaluate the effect of multiple-dose rifampicin (a strong CYP3A4 inducer) and multiple-dose itraconazole (a strong CYP3A4 inhibitor) on the single-dose pharmacokinetics of MDR-001, an oral small-molecule GLP-1 receptor agonist being developed for weight management. The study plans to enroll 28 healthy Chinese adults (18-55 years, BMI 18-28 kg/m²), with 12 participants in Part A (rifampicin) and 16 in Part B (itraconazole). The primary outcomes are the effects of rifampicin and itraconazole on Cmax, AUC0-t, and AUC0-∞ of MDR-001. Secondary outcomes include safety and tolerability (adverse events, vital signs, ECG, laboratory tests) and comparison of other pharmacokinetic parameters (Tmax, t1/2, MRT, CL/F, Vd/F, λz) between MDR-001 alone and combined with the interacting drugs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Voluntary participation and signed informed consent before any study procedures, with full understanding of the study content, procedures, and potential adverse reactions.
- •Healthy Chinese adult males or females aged 18 to 55 years (inclusive).
- •Body weight ≥50 kg for males and ≥45 kg for females, and body mass index (BMI) between 18 and 28 kg/m² (inclusive).
- •Judged by the investigator to be in good health, with medical history, laboratory tests, physical examination, vital signs, and ECG results being normal or abnormal without clinical significance.
- •Participants and their partners must have no pregnancy plan and agree to use effective non-drug contraceptive measures (e.g., condoms, non-medicated intrauterine devices) from 2 weeks before screening until 6 months after the end of the study, unless permanent sterilization has been performed (e.g., bilateral tubal ligation, vasectomy).
- •Willing to comply with the visit schedule, study treatment, laboratory tests, and other study-related procedures and requirements as specified in the protocol.
排除标准
- •Average daily smoking >5 cigarettes within 3 months before dosing.
- •History of headaches (e.g., migraine, tension-type headache).
- •Allergic constitution (multiple drug or food allergies) or intolerance/allergy to the active ingredient or excipients of the study drugs.
- •History of alcohol abuse (≥14 units of alcohol per week; 1 unit = 285 mL beer, 25 mL spirits, or 100 mL wine).
- •History of drug abuse or use of illicit drugs within 5 years before dosing.
- •Blood donation or significant blood loss (≥400 mL) within 3 months before dosing, or planned blood donation during the study.
- •Any disease that increases bleeding risk, such as acute gastritis or gastric/duodenal ulcer.
- •Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2), or genetic conditions predisposing to MTC.
- •History of pancreatitis or symptomatic gallbladder disease.
- •Serum calcitonin > upper limit of normal (ULN) at screening.
- •Dysphagia, or gastrointestinal disorders affecting absorption (e.g., diarrhea, vomiting, inflammatory bowel disease, active ulcer), or history of gastrointestinal surgery leading to malabsorption, or long-term use of drugs affecting gastrointestinal motility (e.g., bariatric surgery such as gastric banding).
- •Special dietary requirements and unable to accept standardized meals.
- •Surgery within 3 months before dosing, or planned surgery during the study, or surgery that affects drug absorption, distribution, metabolism, or excretion.
- •Received live attenuated vaccine within 1 month before dosing, or planned vaccination during the study.
- •Use of any prescription drug, over-the-counter drug, vitamin product, or herbal medicine within 14 days before dosing.
- •Significant changes in diet or exercise habits within 3 months before dosing.
- •Use of CYP3A4 inhibitors, CYP3A4 inducers, or P-gp inhibitors within 14 days before the first dose, or planned use during the study.
- •Participation in another clinical trial or receipt of an investigational drug within 3 months before dosing (unless the participant withdrew before treatment/randomization).
- •ECG abnormalities with clinical significance at screening; QTcF >450 msec (males) or >470 msec (females) by Fridericia's correction.
- •Pregnant, lactating, or positive pregnancy test in females of childbearing potential.
- •Clinically significant laboratory abnormalities, or clinically significant diseases within 12 months before dosing (respiratory, circulatory, digestive, endocrine, rheumatic/immune, nervous, hematologic, or psychiatric disorders) that make the participant unsuitable for the study.
- •Positive screening for hepatitis B surface antigen, hepatitis C antibody/core antigen, HIV antibody, or syphilis antibody.
- •Acute illness or concomitant medication between screening and first dose.
- •Positive alcohol breath test or urine drug screen.
- •Any other condition judged by the investigator as unsuitable for participation.
研究组 & 干预措施
Part A (Rifampin Arm)
Participants receive a single oral dose of MDR-001 alone on Day 1. then rifampin from Day 3 to Day 11, with a second single dose of MDR-001 co-administered on Day 10.
干预措施: MDR-001 (Drug)
Part A (Rifampin Arm)
Participants receive a single oral dose of MDR-001 alone on Day 1. then rifampin from Day 3 to Day 11, with a second single dose of MDR-001 co-administered on Day 10.
干预措施: Rifampin (Drug)
Part B (Itraconazole Arm)
Participants receive a single oral dose of MDR-001alone on Day 1. , then receive itraconazole once daily from Day 3 to Day 8, with a second single dose of MDR-001 co-administered on Day 7.
干预措施: MDR-001 (Drug)
Part B (Itraconazole Arm)
Participants receive a single oral dose of MDR-001alone on Day 1. , then receive itraconazole once daily from Day 3 to Day 8, with a second single dose of MDR-001 co-administered on Day 7.
干预措施: Itraconazole (Drug)
结局指标
主要结局
Cmax of MDR-001
时间窗: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
Maximum observed plasma concentration of MDR-001 after single-dose administration alone and in combination with rifampin (Part A) or itraconazole (Part B).
AUC0-t of MDR-001
时间窗: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
Area under the plasma concentration-time curve from time zero to the last measurable concentration after single-dose administration alone and in combination.
AUC0-∞ of MDR-001
时间窗: Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).
Area under the plasma concentration-time curve from time zero extrapolated to infinity after single-dose administration alone and in combinatio
次要结局
- Other Pharmacokinetic Parameters of MDR-001(Baseline (Day 1 pre-dose) and up to 48 hours post-dose on Day 1 and on co-administration (Day 10 for Part A, Day 7 for Part B).)
- Safety and Tolerability - Adverse Events(From first dose of study drug (Day 1) through follow-up phone call (Day 19 ±2 for Part A, Day 16 ±2 for Part B).)
- Safety and Tolerability - Clinical Laboratory Tests(Screening, Day -1, Day 3, Day 6 (Part A only), Day 10 or 7 (co-administration day), and Day 12 or 9 (discharge) or early termination.)
- Safety and Tolerability - 12 Lead ECG(Screening, Day -1, Day 1 (pre-dose and 2h post-dose), Day 3, Day 6 (Part A), Day 10 or 7 (pre-dose and 2h post-dose), Day 12 or 9, and early termination.)
- Safety and Tolerability - 12-Lead ECG(Screening, Day -1, Day 1 (pre-dose and 2h post-dose), Day 3, Day 6 (Part A), Day 10/7 (pre-dose and 2h post-dose), Day 12/9, and early termination.)
- Safety and Tolerability - Vital Signs(Screening, Day -1, Day 1 and co-administration day (pre-dose, 2h and 6h post-dose), Day 2, Day 3-9 or 11 (daily), Day 12 or 9, and early termination.)
- Safety and Tolerability - Physical Examination(Screening, Day -1, Day 3, co-administration day (Day 10 or 7), Day 12 or 9, and early termination.)