Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of Rifasutenizol (TNP 2198) in Combination With Rabeprazole and Amoxicillin in the Primary Treatment of Participants With H. Pylori Infection
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 700
- 试验地点
- 1
- 主要终点
- Eradication Rate of H.Pylori Infection
研究概览
简要总结
A multi-center, randomized, double-blind, bismuth-containing quadruple active comparator-controlled Phase 3 clinical study to evaluate the efficacy and safety of Rifasutenizol in combination with rabeprazole and amoxicillin in the primary treatment of participants with H. pylori infection using an adaptive design with sample size re-estimation.
详细描述
Subjects will be randomly assigned to test group or control group at a 1:1 ratio stratified by study site, and will receive Rifasutenizol capsules, rabeprazole sodium enteric-coated tablets, amoxicillin capsules combined with clarithromycin placebo tablets and bismuth potassium citrate placebo capsules (test group), or bismuth-containing quadruple regimen of amoxicillin capsules, clarithromycin tablets, rabeprazole sodium enteric-coated tablets and bismuth potassium citrate capsules combined with Rifasutenizol placebo capsules (control group) for 14 consecutive days.
carbon-13 (13C) UBT will be performed 4-6 weeks after the last dose to evaluate the eradication effect of H. pylori.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign the informed consent form.
- •Age 18-65 years (inclusive), male or female.
- •The result of 13C-UBT is positive (≥ 4 Delta Over Baseline), and the infection of H. pylori are confirmed by gastroscopic biopsy histology.
- •Subjects agree to refrain from taking any antibiotics or traditional Chinese medicines with antibacterial effect, bismuth, and antacids (such as proton pump inhibitor, H2 receptor blocker, P-CAB) other than the study drugs during the Screening Period until the end of the study (Visit 5, i.e., Efficacy Evaluation Visit).
- •Subjects and their heterosexual partners must agree to have no pregnancy plan and voluntarily take effective contraceptive measures during the trial and for at least 6 months after the end of the study medication.
- •Willing to follow and able to complete all trial procedures.
排除标准
- •Allergy to any of the study drugs (rabeprazole, amoxicillin, clarithromycin, bismuth potassium citrate), allergic constitution (multiple drug and food allergies); or any contraindication to the use of rifamycin, nitroimidazoles or study drugs.
- •History of H. pylori eradication therapy (including participation in other clinical trials for H. pylori eradication).
- •Subjects with confirmed tuberculosis (TB) or Mycobacterium avium complex (MAC) infection or a history of TB or MAC infection.
- •History of dysphagia or any gastrointestinal disorder affecting drug absorption.
- •History of obstruction pyloric; or excessive gastric acid secretion (such as Zollinger-Ellison syndrome).
- •History of gastric cancer.
- •History of neoplasm malignant within 5 years prior to screening, with the exception of basal cell carcinoma or carcinoma cervix in situ treated without evidence of recurrence.
- •History of esophageal or gastric surgery, except for simple repair of the perforated ulcer.
- •History of substance abuse or drug use within 5 years prior to screening.
- •Alcohol abuse or a history of alcohol abuse within 5 years prior to screening (average weekly consumption of ≥ 14 units of alcohol: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine/Chinese rice wine/rice wine);
- •Presence of active gastric and/or duodenal ulcer.
- •Anticoagulant therapy or long-term treatment with nonsteroidal anti-inflammatory drugs.
- •Treatment with any other investigational new drugs within 4 weeks prior to the Screening Period.
- •Any prohibited medications or non-drug therapies as specified in the protocol (see Section 10.3).
- •White blood cell count or neutrophil count below the lower limit of normal range.
- •Anemia (hemoglobin < 90 g/L).
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, or serum creatinine above the upper limit of normal range.
- •Test positive for hepatitis B surface antigen, hepatitis C antibody, AIDS antibody, or microspironema pallidum antibody.
- •Abnormal ECG with clinical significance.
- •Female subjects who are pregnant, lactating, or have a positive urine pregnancy result during the Screening Period.
- •Inability to communicate with the Investigator and to comply with the study requirements.
- •Other conditions considered inappropriate to participate in this study by the Investigator, e.g., the subject has a history of severe central nervous system, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urological, endocrine, or hematological diseases, or has clinical manifestations of these diseases.
研究组 & 干预措施
Control Group
Amoxicillin capsules 1 g + Clarithromycin tablets 500 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Bismuth potassium citrate capsules 240 mg + Rifasutenizol placebo capsules, BID for 14 days
干预措施: Rifasutenizol placebo capsules (Drug)
Test Group
Rifasutenizol capsules 400 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Amoxicillin capsules 1 g + Bismuth potassium citrate placebo capsules + Clarithromycin placebo tablets, twice daily (BID) for 14 days
干预措施: Rifasutenizol capsules (Drug)
Test Group
Rifasutenizol capsules 400 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Amoxicillin capsules 1 g + Bismuth potassium citrate placebo capsules + Clarithromycin placebo tablets, twice daily (BID) for 14 days
干预措施: Rabeprazole sodium enteric-coated tablets (Drug)
Test Group
Rifasutenizol capsules 400 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Amoxicillin capsules 1 g + Bismuth potassium citrate placebo capsules + Clarithromycin placebo tablets, twice daily (BID) for 14 days
干预措施: Amoxicillin Capsules (Drug)
Test Group
Rifasutenizol capsules 400 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Amoxicillin capsules 1 g + Bismuth potassium citrate placebo capsules + Clarithromycin placebo tablets, twice daily (BID) for 14 days
干预措施: Clarithromycin placebo tablets (Drug)
Test Group
Rifasutenizol capsules 400 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Amoxicillin capsules 1 g + Bismuth potassium citrate placebo capsules + Clarithromycin placebo tablets, twice daily (BID) for 14 days
干预措施: Bismuth potassium citrate placebo capsules (Drug)
Control Group
Amoxicillin capsules 1 g + Clarithromycin tablets 500 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Bismuth potassium citrate capsules 240 mg + Rifasutenizol placebo capsules, BID for 14 days
干预措施: Rabeprazole sodium enteric-coated tablets (Drug)
Control Group
Amoxicillin capsules 1 g + Clarithromycin tablets 500 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Bismuth potassium citrate capsules 240 mg + Rifasutenizol placebo capsules, BID for 14 days
干预措施: Amoxicillin Capsules (Drug)
Control Group
Amoxicillin capsules 1 g + Clarithromycin tablets 500 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Bismuth potassium citrate capsules 240 mg + Rifasutenizol placebo capsules, BID for 14 days
干预措施: Clarithromycin tablets (Drug)
Control Group
Amoxicillin capsules 1 g + Clarithromycin tablets 500 mg + Rabeprazole sodium enteric-coated tablets 20 mg + Bismuth potassium citrate capsules 240 mg + Rifasutenizol placebo capsules, BID for 14 days
干预措施: Bismuth potassium citrate capsules (Drug)
结局指标
主要结局
Eradication Rate of H.Pylori Infection
时间窗: 4 to 6 weeks after the last dose of the study drugs
The eradication rate of H. pylori is defined as the percentage of participants with negative results of 13C UBT.
次要结局
- Eradication Rate of Antibiotic-resistant Strains of H.Pylori(4 to 6 weeks after the last dose of the study drugs)
- Safety by Assessment of the Number of Participants With Adverse Events (AEs)(up to 4-6 weeks after the last dose of the study drugs)
- Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Rifasutenizol (TNP-2198) on Day 1(Day 1: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, and 12 hours after Rifasutenizol (TNP-2198) administration)
- Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Rifasutenizol (TNP-2198) on Day 14(Day 14: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Maximum Observed Plasma Concentration (Cmax) of Rifasutenizol (TNP-2198) on Day 1(Day 1: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Maximum Observed Plasma Concentration (Cmax) of Rifasutenizol (TNP-2198) on Day 14(Day 14: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Half Life (t1/2) of Rifasutenizol (TNP-2198) on Day 1(Day 1: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Half Life (t1/2) of Rifasutenizol (TNP-2198) on Day 14(Day 14: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) of Rifasutenizol (TNP-2198) on Day 1(Day 1: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) of Rifasutenizol (TNP-2198) on Day 14(Day 14: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) of Rifasutenizol (TNP-2198) on Day 1(Day 1: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) of Rifasutenizol (TNP-2198) on Day 14(Day 14: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Volume of Distribution (Vd/F) of Rifasutenizol (TNP-2198) on Day 1(Day 1: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Volume of Distribution (Vd/F) of Rifasutenizol (TNP-2198) on Day 14(Day 14: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Clearance (CL/F) of Rifasutenizol (TNP-2198) on Day 1(Day 1: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)
- Clearance (CL/F) of Rifasutenizol (TNP-2198) on Day 14(Day 14: 30 minutes before and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 hours after Rifasutenizol (TNP-2198) administration)