A Single-Dose, Open-label, Pharmacokinetics Study of Lobeglitazone From M107 ODT and Duvie® Under Fasted and Fed Conditions in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and clinically significant abnormalities
研究概览
简要总结
Phase 1 study evaluating the safety, tolerability, and pharmacokinetics of lobeglitazone administered as M107 Orally Disintegrating Tablet and Duvie tablet in healthy adult participants under fasted and fed conditions.
详细描述
This is a Phase 1, single-center, parallel group study designed to determine the single-dose safety and PK profile of lobeglitazone from M107 ODT and Duvie, both administered orally in healthy adult volunteers.
Participants will be enrolled in 1 of 3 cohorts conducted in parallel:
Cohort 1 (Crossover): A single dose of Duvie oral tablet (0.415 mg; fasted) on Day 1 followed by a single dose of M107 ODT (0.4 mg; fasted) on Day 8, or vice versa, based on their random assignment with a 7-day washout between each dose.
Cohort 2 (Crossover): M107 ODT (0.8 mg; fasted) followed by M107 ODT (0.8 mg; fed) after a 7-day washout.
Cohort 3: M107 ODT (1.2 mg fasted) Participants in this cohort will receive M107 ODT 1.2 mg after a 10-hour fast.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female participants aged 18 to 55 years (inclusive) at the time of informed consent.
- •Body Mass Index (BMI) between 18.0 and 30.0 kg/m² (inclusive) at Screening.
- •Body weight ≥50 kg at Screening.
- •Capable of giving informed consent and complying with study procedures.
- •Female participants must be of non-childbearing potential (postmenopausal or surgically sterile) or, if of childbearing potential, must agree to use acceptable contraception.
- •Participants must be non-smokers and must not have used any nicotine-containing products within 30 days prior to Screening and throughout the study.
- •Normal findings in physical examination, clinical laboratory tests, vital signs, and ECG, or findings considered not clinically significant by the investigator.
- •Willing to abstain from alcohol, grapefruit products, and caffeine as per study restrictions.
- •Willing to refrain from strenuous physical activity as specified in the protocol.
- •Male participants must agree to use contraception and avoid sperm donation during the study and for a specified period after.
- •Female participants of childbearing potential must agree to refrain from egg donation during the study and for at least 30 days after the last dose of study drug.
排除标准
- •Pregnant or breastfeeding females, or individuals (male or female) actively trying to conceive.
- •History of drug or alcohol use disorder within the past 2 years.
- •Active smoker or user of nicotine products (>5 cigarettes/week) or positive cotinine test at admission.
- •Difficulty with venipuncture or history of coagulopathy/endocarditis.
- •Significant history of cardiovascular, respiratory, gastrointestinal, renal, hepatic, neurological, endocrine, hematologic, or psychiatric disorders.
- •History of malignancy not in complete remission for at least 5 years (except localized basal/squamous cell skin cancer or prostate cancer deemed controlled).
- •Use of any prescription or over-the-counter medication, vitamins, or herbal supplements within 14 days or 5 half-lives prior to screening.
- •Use of any prescription medication, over-the-counter medication, or herbal supplements (other than permitted contraceptives or as approved by the investigator) from Screening until completion of the study.
- •Elevated resting blood pressure (systolic >140 mmHg or diastolic >90 mmHg) or heart rate >100 bpm.
- •History of major surgery within 4 weeks or minor surgery within 2 weeks of dosing.
- •Recent flu-like illness or respiratory infection within 2 weeks, or recent live-virus vaccination within 4 weeks of dosing.
- •Clinically significant ECG abnormalities including QTcF >450 ms, 2nd/3rd degree atrioventricular block, or incomplete left hemiblock.
- •Known bleeding disorders or history of significant allergic reaction to any drug component used in the study.
- •Blood or plasma donation >500 mL within 30 days before screening.
- •Any other condition which, in the opinion of the investigator, would preclude safe participation.
研究组 & 干预措施
M107-C101 Cohort 1
Participants will receive a single oral dose of either Duvie (0.415 milligrams) or M107 Orally Disintegrating Tablet (0.4 milligrams) under fasted conditions on Day 1, followed by the alternate treatment on Day 8 after a 7-day washout. 8 participants are expected to enroll in this cohort.
干预措施: M107 and Duvie - Cohort 1 (Drug)
M107-C101 Cohort 2
Participants will receive a single 0.8 milligram oral dose of M107 Orally Disintegrating Tablet under fasted conditions on Day 1 and under fed conditions on Day 8, following a 7-day washout. 8 participants are expected to enroll in this cohort.
干预措施: M107 - Cohort 2 (Drug)
M107-C101 Cohort 3
Participants will receive a single 1.2 milligram dose of M107 Orally Disintegrating Tablet under fasted conditions. 8 participants are expected to enroll in this cohort.
干预措施: M107 - Cohort 3 (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and clinically significant abnormalities
时间窗: From screening to follow-up (up to Day 15 post-dose)
To assess the frequency and severity of TEAEs, SAEs, and any clinically significant changes in laboratory parameters, vital signs, electrocardiogram, and physical examination findings following administration of M107 Orally Disintegrating Tablet and Duvie.
Maximum observed plasma concentration (Cmax)
时间窗: From pre-dose to 48 hours post-dose
To determine the peak plasma concentration of Lobeglitazone following oral administration of M107 Orally Disintegrating Tablet and Duvie.
Time to maximum observed plasma concentration (Tmax)
时间窗: From pre-dose to 48 hours post-dose
To assess the time it takes to reach the maximum plasma concentration of Lobeglitazone after administration.
Last measurable plasma concentration (Clast)
时间窗: From pre-dose to 48 hours post-dose
To evaluate the last quantifiable concentration of Lobeglitazone detected in plasma following administration.
Time of last measurable plasma concentration (Tlast)
时间窗: From pre-dose to 48 hours post-dose
To determine the time at which the last quantifiable plasma concentration of Lobeglitazone is observed.
Area under the concentration-time curve from 0 to 24 hours (AUC0-24h)
时间窗: From pre-dose to 24 hours post-dose
To evaluate the extent of Lobeglitazone exposure over the first 24 hours post-dose.
Area under the concentration-time curve from 0 to last measurable concentration (AUC0-last)
时间窗: From pre-dose to 48 hours post-dose
To assess the total plasma exposure to Lobeglitazone from dosing until the last quantifiable concentration.
Area under the concentration-time curve extrapolated to infinity (AUCinf)
时间窗: From pre-dose to 48 hours post-dose
To estimate total drug exposure by including the extrapolated portion of the concentration-time curve.
Percentage of AUC extrapolated (%AUCexp)
时间窗: From pre-dose to 48 hours post-dose
Percentage of the total area under the plasma concentration-time curve from time zero to infinity (AUC₀-inf) that is extrapolated beyond the last measurable concentration (%AUCexp).
Terminal elimination half-life (t½)
时间窗: From pre-dose to 48 hours post-dose
To determine the time required for the plasma concentration of Lobeglitazone to decrease by half during the terminal elimination phase.
Apparent oral clearance (CL/F)
时间窗: From pre-dose to 48 hours post-dose
To assess the rate at which Lobeglitazone is eliminated from the plasma after oral administration.
Apparent volume of distribution (Vz/F)
时间窗: From pre-dose to 48 hours post-dose
To calculate the apparent volume in which Lobeglitazone is distributed throughout the body after oral administration.
Terminal elimination rate constant (λz or Kel)
时间窗: From pre-dose to 48 hours post-dose.
To estimate the terminal elimination rate constant (λz or Kel) from the log-linear terminal phase of the plasma concentration-time curve following oral administration of lobeglitazone.
次要结局
- Effect of food on maximum observed plasma concentration (Cmax) of Lobeglitazone(From pre-dose to 48 hours post-dose)
- Effect of food on time to maximum observed plasma concentration (Tmax) of Lobeglitazone(From pre-dose to 48 hours post-dose)
- Effect of food on total drug exposure (AUC0-last and AUCinf)(From pre-dose to 48 hours post-dose)
- Effect of food on terminal elimination half-life (t½)(From pre-dose to 48 hours post-dose)
- Effect of food on apparent oral clearance (CL/F) and volume of distribution (Vz/F)(From pre-dose to 48 hours post-dose)
- Effect of food on terminal elimination rate constant (λz or Kel) of lobeglitazone(From pre-dose to 48 hours post-dose.)