A Phase 1, Single-center, Double-blind, Placebo-controlled Study to Evaluate Pharmacokinetics (PK) and Preliminary Efficacy of Multiple Oral Administrations of TNP-2092 Capsules in Healthy Subjects With Helicobacter Pylori Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Safety of TNP-2092 by Assessment of the Number of Adverse Events (AEs)
研究概览
简要总结
This study was a single-center, randomized, double-blind, placebo-controlled, dose-ascending multiple-dose-administration study. The aim of this study was to evaluate the safety, tolerability, and pharmacokinetic profile of TNP-2092 Capsules in asymptomatic healthy subjects with Helicobacter pylori infection, and to explore the preliminary efficacy of TNP-2092 Capsules in eradicating Helicobacter pylori.
详细描述
This study was a single-center, randomized, double-blind, placebo-controlled, dose-ascending multiple-dose-administration study. The aim of this study was to evaluate the safety, tolerability, and pharmacokinetic profile of TNP-2092 Capsules in asymptomatic healthy subjects with Helicobacter pylori infection, and to explore the preliminary efficacy of TNP-2092 Capsules in eradicating Helicobacter pylori.
In this study, three dose groups of 100 mg, 300 mg and 600 mg will be set up. The drug will be taken twice a day for 14 consecutive days, and last dose on the morning of Day 15. Fifteen subjects in each of the 100 mg and 300 mg dose groups will be randomized at a ratio of 4:1, with 12 subjects receiving the investigational product and 3 receiving placebo. Ten subjects in the 600 mg dose group will be randomized at a ratio of 4:1, with 8 subjects receiving the investigational product and 2 subjects receiving placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Those who are fully informed of and understand this study and have signed the Informed Consent Form.
- •Those who are willing to follow and able to complete all the trial procedures.
- •Female subjects of childbearing potential must agree to abstinence or take effective contraceptive measures during the trial and at least 70 days (10 weeks) after administration.
- •Male subjects must agree to abstinence or use condoms as a contraceptive measure during the trial and at least 70 days (10 weeks) after administration.
- •Sex: male or female.
- •Age: 18-45 years, including 18 and 45 years.
- •BMI: 19.0-26.0 kg/m2, including 19.0 and 26.0 kg/m
- •Those who do not smoke, or have smoked less than 5 cigarettes per day within 3 months before screening; those who do not drink alcohol, or have drunk less than 14 units of alcohol per week (1 unit of alcohol = 360 mL of beer or 45 mL of spirits with 40% alcohol content or 150 mL of wine) within 6 months before screening; those who have not smoked or drunk alcohol within 48 hours before admission to the study site.
- •Subjects whose clinical laboratory test results are within the normal range or whose test results are abnormal but judged by the investigator to be of no clinical insignificance.
- •Those with a positive 14C urea breath test (UBT) result.
排除标准
- •Those with an allergic constitution, a history of allergic diseases or a history of drug allergy.
- •Those with a history of alcohol or drug abuse in the past 10 years.
- •Those who have donated blood within 3 months before enrollment.
- •Those with regular use of any prescription/over-the-counter drugs, including vitamins, minerals, nutritional supplements or herbs, within 2 weeks before enrollment and during the study period.
- •Those who have taken any drug that changes the activity of liver enzymes 28 days before taking the investigational product or during the study.
- •Those who have participated in any clinical trials within 3 months before enrollment.
- •Those with a history of eradication of Helicobacter pylori.
- •Those who are suffering or have suffered from digestive tract diseases, including digestive tract ulcer, etc.
- •Those with symptoms or past medical history of cardiovascular, respiratory, urinary, neurological, blood, immune, endocrine system diseases or tumor, mental illness, or any situation which, in the opinion of the investigator, may threaten the safety of the subjects or affect the correctness of the trial results.
- •Those whose blood pressure remains above 140/90 mmHg after retest.
- •Pregnant or lactating women.
- •Those who are HIV positive, syphilis positive, hepatitis B surface antigen positive, hepatitis C antibody positive.
- •Those who have had beverages or foods containing methylxanthine (coffee, tea, coke, chocolate, and energy drinks), grapefruit (fruit juice) and alcohol within 48 hours (2 days) before the clinical study.
- •Other circumstances deemed by the investigator to be unsuitable for the subject to participate in this study.
研究组 & 干预措施
TNP-2092 capsules 100 mg
Subjects received TNP-2092 capsules orally twice daily at the dose of 100 mg in the fed state for consecutive 14 days and received the last dose in the fed state on the morning of Day 15
干预措施: TNP-2092 capsules (Drug)
TNP-2092 capsules 300 mg
Subjects received TNP-2092 capsules orally twice daily at the dose of 300 mg in the fed state for consecutive 14 days and received the last dose in the fed state on the morning of Day 15
干预措施: TNP-2092 capsules (Drug)
TNP-2092 capsules 600 mg
Subjects received TNP-2092 capsules orally twice daily at the dose of 600 mg in the fed state for consecutive 14 days and received the last dose in the fed state on the morning of Day 15
干预措施: TNP-2092 capsules (Drug)
Placebo
Subjects received TNP-2092 placebo capsules orally twice daily in the fed state for consecutive 14 days and received the last dose in the fed state on the morning of Day 15
干预措施: Placebo (Drug)
结局指标
主要结局
Safety of TNP-2092 by Assessment of the Number of Adverse Events (AEs)
时间窗: Day 1 to Day 49
An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
Area Under the Plasma Concentration Versus Time Curve Over a Dosing Interval (AUC0-tau) on Day 1
时间窗: Day 1：Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Maximum Observed Plasma Concentration (Cmax) of TNP-2092 on Day 1
时间窗: Day 1：Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Time to Reach the Maximum Observed Plasma Concentration (Tmax) on Day 1
时间窗: Day 1：Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Maximum Observed Plasma Concentration (Cmax) of TNP-2092 on Day 15
时间窗: Day 15: Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Time to Reach the Maximum Observed Plasma Concentration (Tmax) Day 15
时间窗: Day 15: Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Half Life (t1/2) of TNP-2092 on Day 15
时间窗: Day 15: Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) on Day 15
时间窗: Day 15: Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Area Under the Plasma Concentration Versus Time Curve From the First Administration to the Last Measurable Plasma Concentration (AUC0-last) on Day 15
时间窗: Day 15: Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Area Under the Plasma Concentration Versus Time Curve Over a Dosing Interval (AUC0-tau) on Day 15
时间窗: Day 15: Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma PK parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.
Number of Participants With Negative Results of 14 Urea Breath Test (14C UBT) at 4 to 6 Weeks After Last Dose
时间窗: Four to 6 weeks after the last dose of the study drugs.
Participants received 14 urea breath test \[14C UBT\] at 4 to 6 weeks after last dose.
Accumulation Index Rac (AUC) of TNP-2092
时间窗: Day 1：Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after administration. Day 15: Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Rac (AUC) is calculated from the ratio of AUC0-tau (Day 15) to AUC0-tau(Day 1).
Accumulation Index Rac(Cmax) of TNP-2092
时间窗: Day 1：Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after administration. Day 15: Before administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after administration
Plasma concentrations of TNP-2092 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2092 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Rac (Cmax) is calculated from the ratio of Cmax (Day 15) to Cmax (Day 1).
次要结局
未报告次要终点