A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of TNP-2198 Capsules in Asymptomatic Participants With Helicobacter Pylori Infection

Study Overview
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Brief Summary
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This study was a Phase 1, single-center, randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and preliminary Helicobacter Pylori eradication efficacy of TNP-2198 capsules.

Official Title
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A Phase 1, Single-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Multiple Oral Doses of TNP-2198 Capsules in Asymptomatic Subjects With Helicobacter Pylori Infection

Conditions
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Helicobacter Pylori Infection

Intervention / Treatment
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* Drug: TNP-2198
* Drug: TNP-2198 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Those signed the informed consent form and fully understood the study contents, process and possible adverse reactions before participation in the study; Those are able to complete the study according to the requirements in the study protocol; Those (including the partner) are willing to use effective contraceptions from the screening up to 6 months after the last dose of study drug; Male and female subjects aged 18-55 years (inclusive); Male subjects no less than 50 kg and female subjects no less than 45 kg. Body mass index (BMI) = body weight (kg)/height2 (m2); BMI: 18-28kg/m2 (inclusive); Health status: no clinically significant history of heart, liver, kidney, digestive tract, nervous system, respiratory system diseases, mental disorders or metabolic abnormalities; Normal results or clinically insignificant abnormal results in physical examinations and vital sign assessment; Positive result of 14C urea breath test (UBT). Exclusion Criteria: Average daily consumption of more than 5 cigarettes within 3 months before the study; Allergic constitution (allergy to multiple drugs and food); History of drug and/or alcohol abuse (mean consumption of ≥ 14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of liquor, or 100 mL of wine); History of Helicobacter Pylori eradication; Blood donation or massive blood loss (> 450 mL) within 3 months prior to screening; Using any drug that changes liver enzyme activity within 28 days prior to screening; Using any prescription drug, over-the-counter drug, any vitamin product, or herbal medicine within 14 days prior to screening; Taking special diet (including dragon fruit, mango, grapefruit, etc.) or strenuous exercise, or having other factors that affect drug absorption, distribution, metabolism, excretion, etc., within 2 weeks prior to screening; Significant changes in diet or exercise habits recently; Administration of any other study drug or participation in any drug clinical study within 3 months before administration of the study drug; With difficulty in swallowing or history of any gastrointestinal diseases that affect drug absorption; With any disease that increases the risk of bleeding, such as hemorrhoids, acute gastritis or gastric and duodenal ulcers; With clinically significant ECG abnormalities; Female subjects who are lactating or having positive serum pregnancy test during screening or during the study; With symptoms or previous history of cardiovascular, digestive, respiratory, urinary, neurological, hematologic, immunological, endocrine system diseases, tumor, or psychiatric diseases; Clinically significant abnormalities in clinical laboratory tests, or other clinically significant findings (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, neoplastic, pulmonary, immunological, psychiatric, or cardiovascular disease); Positive viral hepatitis (including hepatitis B and C), HIV antigen/antibody, treponema pallidum antibody; Acute illness or concomitant medication from the time of signing the informed consent to the time of study medication; Intake of chocolate, any caffeine- or xanthine-containing food or drink within 48 hours prior to administration of study drug; Intake of any alcohol-containing product within 48 hours before administration of study drug; Positive urine drug screening or history of drug abuse or drug addiction within the past 5 years; Other conditions that, in the opinion of the investigator, make the patient participating in this study inappropriate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multiple Ascending Doses Cohort 1<br>TNP-2198 Capsules 200mg, BID, for 14days | Drug: TNP-2198<br>* TNP-2198 capsules/placebo were administered orally twice daily (BID, at 7:00 ± 1 hour in the morning and 19:00 ± 1 hour in the evening) in the fasted state for consecutive 14 days, and the last dose was taken at 7:00 am (±1 hour) on Day 15 in the fasted state, and breakfast or dinner should not be taken within 30 minutes after each dose.<br>* Other names: Rifasutenizol;Drug: TNP-2198 Placebo<br>* TNP-2198 capsules/placebo were administered orally twice daily (BID, at 7:00 ± 1 hour in the morning and 19:00 ± 1 hour in the evening) in the fasted state for consecutive 14 days, and the last dose was taken at 7:00 am (±1 hour) on Day 15 in the fasted state, and breakfast or dinner should not be taken within 30 minutes after each dose.<br>|
| Experimental: Multiple Ascending Doses Cohort 2<br>TNP-2198 Capsules 400mg,BID, for 14days | Drug: TNP-2198<br>* TNP-2198 capsules/placebo were administered orally twice daily (BID, at 7:00 ± 1 hour in the morning and 19:00 ± 1 hour in the evening) in the fasted state for consecutive 14 days, and the last dose was taken at 7:00 am (±1 hour) on Day 15 in the fasted state, and breakfast or dinner should not be taken within 30 minutes after each dose.<br>* Other names: Rifasutenizol;Drug: TNP-2198 Placebo<br>* TNP-2198 capsules/placebo were administered orally twice daily (BID, at 7:00 ± 1 hour in the morning and 19:00 ± 1 hour in the evening) in the fasted state for consecutive 14 days, and the last dose was taken at 7:00 am (±1 hour) on Day 15 in the fasted state, and breakfast or dinner should not be taken within 30 minutes after each dose.<br>|
| Experimental: Multiple Ascending Doses Cohort 3<br>TNP-2198 Capsules 600mg,BID, for 14days | Drug: TNP-2198<br>* TNP-2198 capsules/placebo were administered orally twice daily (BID, at 7:00 ± 1 hour in the morning and 19:00 ± 1 hour in the evening) in the fasted state for consecutive 14 days, and the last dose was taken at 7:00 am (±1 hour) on Day 15 in the fasted state, and breakfast or dinner should not be taken within 30 minutes after each dose.<br>* Other names: Rifasutenizol;Drug: TNP-2198 Placebo<br>* TNP-2198 capsules/placebo were administered orally twice daily (BID, at 7:00 ± 1 hour in the morning and 19:00 ± 1 hour in the evening) in the fasted state for consecutive 14 days, and the last dose was taken at 7:00 am (±1 hour) on Day 15 in the fasted state, and breakfast or dinner should not be taken within 30 minutes after each dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events(AEs) | The percentage of subjects with at least one AEs. | up to 17 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-Time Curve from the First Dose Extrapolated to Infinity (AUC0-∞) | Plasma concentrations of TNP-2198 were measured by a specific and validated assay. Plasma Pharmacokinetics (PK) parameters of TNP-2198 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. | Day 1,Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 14, Day 15 | 
| Area Under the Plasma Concentration-Time Curve from the First Dose to the Last Measurable Concentration (AUC 0-last) | Plasma concentrations of TNP-2198 were measured by a specific and validated assay. Plasma PK parameters of TNP-2198 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. | Day 1,Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 14, Day 15 | 
| Maximum Observed Plasma Concentration (Cmax) of TNP-2198 | Plasma concentrations of TNP-2198 were measured by a specific and validated assay at specified time points | Day 1,Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 14, Day 15 |