Efficacy and Safety of Rifasutenizol (TNP 2198), Rabeprazole and Amoxicillin in Participants With H. Pylori Infection

TenNor Therapeutics (Suzhou) Limited700 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

700

Conditions

H.Pylori Infection

Interventions

Rifasutenizol capsulesDRUG

400 mg, BID, taken orally within half an hour after breakfast and dinner.

Rabeprazole sodium enteric-coated tabletsDRUG

20 mg, BID, taken orally within half an hour before breakfast and dinner.

Amoxicillin CapsulesDRUG

1 g, BID, taken orally within half an hour after breakfast and dinner.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Locations (1)

Peking University Third Hospital

Beijing, China

Outcomes

Primary Outcomes

Eradication Rate of H.Pylori Infection

The eradication rate of H. pylori is defined as the percentage of participants with negative results of 13C UBT.

Time frame: 4 to 6 weeks after the last dose of the study drugs

Secondary Outcomes

Eradication Rate of Antibiotic-resistant Strains of H.Pylori

Percentage of Participants with Successful Helicobacter Pylori (H.pylori) Eradication in Participants with antibiotic-resistant Strains of H.pylori at Baseline (based on the test results of 13C UBT)

Time frame: 4 to 6 weeks after the last dose of the study drugs

Safety by Assessment of the Number of Participants With Adverse Events (AEs)

An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events.

Time frame: 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

Plasma concentrations of Rifasutenizol (TNP-2198) were measured by a specific and validated assay. Plasma pharmacokinetic (PK) parameters of Rifasutenizol (TNP-2198) were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.

Time frame: 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

Data from ClinicalTrials.gov

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BID, taken orally within half an hour after breakfast and dinner.

Bismuth potassium citrate placebo capsulesDRUG

BID, taken orally within half an hour before breakfast and dinner.

Clarithromycin tabletsDRUG

500 mg, BID, taken orally within half an hour after breakfast and dinner.

Bismuth potassium citrate capsulesDRUG

240 mg, BID, taken orally within half an hour before breakfast and dinner.

Rifasutenizol placebo capsulesDRUG

BID, taken orally within half an hour before breakfast and dinner.

Plasma concentrations of Rifasutenizol (TNP-2198) were measured by a specific and validated assay. Plasma PK parameters of Rifasutenizol (TNP-2198) were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods.