A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Food Effect of TNP-2198 Capsules After Single Oral Dose in Healthy Participants

A Single-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase 1 Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of a Single Oral Dose of TNP-2198 Capsules in Healthy Participants and the Effect of Food on the Pharmacokinetics of TNP-2198 Capsules in Healthy Participants

This was a single-center, randomized, double-blind, placebo-controlled phase 1 study to evaluate the safety, tolerability, pharmacokinetics of single ascending dose and the food effect on the pharmacokinetics of TNP-2198 capsules after single dose oral administration in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: TNP-2198; Drug: TNP-2198 Placebo

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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 of the study protocol;
• Those (including the partner) are willing to use effective contraceptives from the screening up to 6 months after the last dose of study drug;
• Male and female subjects aged 18 to 55 years (inclusive);
• Male subjects no less than 50 kg and female subjects no less than 45 kg. BMI (Body Mass Index= body weight (kg)/height^2 (m^2)): 18-28kg/m^2 (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 abnormal results without clinical significance in physical examinations and vital signs;
• Clinical laboratory test results are within normal limits or abnormal but without clinical significance as judged by the investigator.

Exclusion Criteria:

• Average daily consumption of more than 5 cigarettes within 3 months before the study;
• History of hypersensitivity to study drug or its excipients, or 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);
• 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;
• Taking other study drugs or participating in other clinical studies within 3 months before taking 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;
• Unable to tolerate standardized meal (two boiled eggs, one butter bacon toast, one box of fried potato chips, and one cup of whole milk) (only for subjects participating in the food effect study);
• With clinically significant ECG abnormalities;
• Female subjects who are lactating or have positive serum pregnancy result during the screening period, or have positive serum pregnancy result 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 antibody, treponema pallidum antibody;
• Acute illness or concomitant medication from the time of signing 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 products within 48 hours prior to 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Doses Cohort 1; TNP-2198 Capsules 50mg	Drug: TNP-2198; Oral; Other Names: Rifasutenizol
Experimental: Single Ascending Doses Cohort 2; TNP-2198 Capsules 100mg	Drug: TNP-2198; Oral; Other Names: Rifasutenizol
Experimental: Single Ascending Doses Cohort 3; TNP-2198 Capsules 200mg	Drug: TNP-2198; Oral; Other Names: Rifasutenizol
Experimental: Single Ascending Doses Cohort 4; TNP-2198 Capsules 400mg	Drug: TNP-2198; Oral; Other Names: Rifasutenizol
Experimental: Single Ascending Doses Cohort 5; TNP-2198 Capsules 600mg	Drug: TNP-2198; Oral; Other Names: Rifasutenizol
Experimental: Single Ascending Doses Cohort 6; TNP-2198 Capsules 800mg	Drug: TNP-2198; Oral; Other Names: Rifasutenizol
Experimental: Single Ascending Doses Cohort 7; TNP-2198 Capsules 1000mg	Drug: TNP-2198; Oral; Other Names: Rifasutenizol
Experimental: Food Effect Cohort 8; TNP-2198 Capsules 200mg	Drug: TNP-2198; Oral; Other Names: Rifasutenizol
Placebo Comparator: Placebo Cohort 9; Placebo	Drug: TNP-2198 Placebo; The placebo for TNP-2198 active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage 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.	Day 1 to Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)	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.	Hour 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 after administration.
Area Under the Plasma Concentration Versus Time Curve from 0 to the Last Measurable Concentration (AUC0-t)	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.	Hour 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 after administration.
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	Hour 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 after administration.

Collaborators and Investigators

• Sponsor: TenNor Therapeutics (Suzhou) Limited
• Investigators: Study Director: TenNor Clinical Trials, TenNor

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2019
• Primary Completion (Actual): September 18, 2019
• Study Completion (Actual): September 18, 2019

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: October 7, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 7, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: TNP-2198-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No