A Randomized, Open-label, Multiple Dosing, Cross-over Phase 1 Clinical Trial to Evaluate Pharmacokinetics/Pharmacodynamics and Safety/Tolerability of IN-C005 and IN-A001 After Oral Administration in Healthy Caucasian Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Cmax
研究概览
简要总结
The purpose of this study is to evaluate pharmacokinetics/pharmacodynamics and safety/tolerability of IN-C005 and IN-A001 after oral administration in healthy Caucasian subjects.
详细描述
[Part 1] To evaluate the pharmacokinetic (PK)/pharmacodynamic (PD) profiles and safety/tolerability of 100 mg IN-C005 versus 100 mg IN-A001 after multiple oral dosing in healthy Caucasian subjects
[Part 2] To evaluate the PK/PD profiles and safety/tolerability of 50 mg IN-C005 versus 75 mg IN-C005 after multiple oral dosing in healthy Caucasian subjects
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
- 19 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Is healthy Caucasian adult aged 19 to 50 years (inclusive) at the time of signing the informed consent form (ICF) (A Caucasian is defined as a European who was born in Europe, has the duration of residence outside of Europe less than 10 years, and both of whose parents and grandparents are European-born).
- •Has ≥ 18.0 and ≤ 30.0 kg/m2 of body mass index (BMI) with a body weight (BW) ≥ 55.0 kg at screening.
- •Has a negative result in serum Helicobacter pylori IgG antibody test.
- •Decides to participate voluntarily in the study after being fully informed of and understanding the study completely, and provides his/her written informed consent prior to screening procedure.
- •Is eligible for this study in the opinion of the investigator based on the results of physical examination, clinical laboratory tests, interview, etc.
排除标准
- •Has a history or current evidence of clinically significant disorder of hepatic, renal, nervous, respiratory, endocrine, hemato-oncologic, cardiovascular, urinary, and/or psychiatric system.
- •Has a history or current evidence of gastrointestinal disease that may affect the safety and PD assessments for study treatment (e.g., gastrointestinal ulcer, gastritis, gastric cramp, gastroesophageal reflux disease, and Crohn's disease) or a history of gastrointestinal surgery (except for simple appendectomy or herniotomy).
- •Has a history or current evidence of clinically significant hypersensitivity to study drugs or any ingredient of proton pump inhibitors and other drugs (such as aspirin and antibiotics).
- •Has a positive result on serology tests (for hepatitis B, human immunodeficiency virus [HIV], and hepatitis C).
- •Has a blood level of total bilirubin, AST (GOT), or ALT (GPT) > 1.5 X upper limit of normal (ULN) based on screening procedures including repeated ones.
- •Has a calculated eGFR per MDRD equation < 60 mL/min/1.73 m2 based on screening procedures including repeated ones.
- •Has systolic blood pressure (SBP) of < 90 mmHg or > 140 mmHg, diastolic blood pressure (DBP) of < 50 mmHg or > 95 mmHg, or pulse rate (PR) of < 45 beats/min or > 100 beats/min on vital signs as measured in sitting position after taking a rest for at least 5 minutes at screening.
- •Has an anatomical disorder that precludes insertion and maintenance of intragastric pH meter catheter or is expected to be intolerable to insertion of intragastric pH meter catheter.
- •Has a history of drug abuse or has a positive response to drug abuse on urine drug screening test.
- •Has received any prescription drug or herbal medication within 2 weeks of or any over-the-counter (OTC) drug, dietary supplements, or vitamins within 1 week of scheduled first dose or is expected to receive such medication during the study (Note: a subject may participate in the study at the discretion of the investigator provided the subject meets all the other criteria).
- •Has participated and received an investigational agent in another clinical trial or bioequivalence study within 6 months prior to the first dose of study treatment (Note: This is not applied to participation in another part of this study).
- •Has donated whole blood within 2 months prior to the scheduled first dose, or has donated blood components or received transfusion within a month prior to the scheduled first dose.
- •Has excessive caffeine intake (> 5 units/day), continues the use of alcohol (> 21 units/week, 1 unit = 10 g of pure alcohol), or is unable to stop drinking during hospitalization period.
- •Has a positive result for cotinine on urine drug screening test or is unable to stop smoking throughout the study.
- •Is unable to avoid grapefruit-containing foods during the time from 24 hours (hrs) before hospitalization to discharge in Period 1 and Period 2, respectively.
- •Is unable to avoid caffeine-containing foods (e.g., coffee, tea [red tea, green tee, etc.], soda, coffee milk, and nutritive tonic drink) during the time from 24 hrs before hospitalization to discharge Period 1 and Period 2, respectively.
- •For all women of childbearing potential (WOCBP) excluding those on amenorrhea for at least 12 months and those who underwent surgical sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), has a positive result for pregnancy test (urine hCG) performed prior to the first dose of study treatment or is pregnant or breastfeeding.
- •Is unable to use a medically acceptable contraceptive method throughout the study. Medically acceptable contraceptive methods include:
- •Use of an intrauterine device with a proven birth control failure rate by the subject or subject's spouse (or partner)
- •Use of (male or female) barrier method with spermicide
- •Surgical sterilization (vasectomy, salpingectomy, tubal ligation, hysterectomy) of the subject or subject's spouse (or partner)
- •Is determined ineligible for study participation by the investigator for other reasons such as clinical laboratory abnormalities.
研究组 & 干预措施
Treatment AB
Participants will be randomized to receive IN-C005 Y mg (Treatment A) and IN-A001 Y mg (Treatment B) sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
干预措施: IN-A001 Y mg (Drug)
Treatment AB
Participants will be randomized to receive IN-C005 Y mg (Treatment A) and IN-A001 Y mg (Treatment B) sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
干预措施: IN-C005 Y mg (Drug)
Treatment BA
Participants will be randomized to receive IN-A001 Y mg and IN-C005 Y mg sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
干预措施: IN-A001 Y mg (Drug)
Treatment BA
Participants will be randomized to receive IN-A001 Y mg and IN-C005 Y mg sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
干预措施: IN-C005 Y mg (Drug)
Treatment CD
Participants will be randomized to receive IN-C005 Z mg (Treatment C) and IN-C005 X mg (Treatment D) sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
干预措施: IN-C005 X mg (Drug)
Treatment CD
Participants will be randomized to receive IN-C005 Z mg (Treatment C) and IN-C005 X mg (Treatment D) sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
干预措施: IN-C005 Z mg (Drug)
Treatment DC
Participants will be randomized to receive IN-C005 X mg and IN-C005 Z mg sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
干预措施: IN-C005 X mg (Drug)
Treatment DC
Participants will be randomized to receive IN-C005 X mg and IN-C005 Z mg sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
干预措施: IN-C005 Z mg (Drug)
结局指标
主要结局
Cmax
时间窗: Day 1, Day 22
PK: Maximum concentration of drug in plasma
Change from baseline in percent duration of pH ≥4 in 24 hrs
时间窗: Day 1, Day 7, Day 22, Day 28
PD: pH parameter
AUClast
时间窗: Day 1, Day 22
PK: Area under the plasma drug concentration-time curve from 0 to last point of measurable concentration
AUCtau,ss
时间窗: Day 7 and Day 28
PK: Area under the plasma drug concentration-time curve for a dosing interval at steady state
Cmax,ss
时间窗: Day 7 and Day 28
PK: Maximum (peak) steady-state plasma drug concentration during a dosage interval
Percent duration of pH ≥4 in 24 hrs (duration %)
时间窗: Day 7, Day 28
PD: pH parameter
次要结局
- CL/F(Day 1, Day 22)
- Vd/F(Day 1, Day 22)
- t1/2,ss(Day 7, Day 28)
- Change from baseline in percent duration of pH ≥3 in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- AUCinf(Day 1, Day 22)
- Tmax(Day 1, Day 22)
- Tmax,ss(Day 7, Day 28)
- Cmin,ss(Day 7, Day 28)
- CLss/F(Day 7, Day 28)
- Gmax(Day 1, Day 7, Day 22, Day 28)
- t1/2(Day 1, Day 22)
- Cavg,ss(Day 7, Day 28)
- Vd,ss/F(Day 7, Day 28)
- PTF(Day 7, Day 28)
- R(Day 7, Day 28)
- Percent duration of pH ≥6 in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Mean and median pH in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Percent duration of pH ≥3 in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Change from baseline in percent duration of pH ≥6 in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Change from baseline in median pH in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Change from baseline in mean pH in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- AUEGlast(Day 1, Day 7, Day 22, Day 28)
- ΔAUEGlast(Day 1, Day 7, Day 22, Day 28)
- ΔGmax(Day 1, Day 7, Day 22, Day 28)