A Phase 1, Single-center, Double-blind, Placebo-controlled Study of TNP-2092 Capsules, and the Food Effect Study After Single-dose Oral Administration of TNP-2092 Capsules

A Phase 1, Single-center, Double-blind, Placebo-controlled Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TNP-2092 Capsules, and the Food Effect on the Pharmacokinetics of TNP-2092 Capsules After Single-dose Oral Administration in Healthy Subjects

The aim of this study is to evaluate the safety, tolerability, and pharmacokinetic characteristics of TNP-2092 Capsules in liver cirrhosis patients with hyperammonemia; and to preliminarily observe the effects of the study drug on blood ammonia and hepatic encephalopathy related clinical symptoms and signs, neuropsychological indicators, and quality of life in liver cirrhosis patients with hyperammonemia.

Study Overview

• Status: Completed
• Conditions: Hyperammonemia
• Intervention / Treatment: Drug: TNP-2092; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 58
• 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:

• Sex: male or female;
• Age: 18-45 years, inclusive;
• BMI: 19.0-26.0 kg/m2, inclusive;
• Female subjects of childbearing potential must agree to practice abstinence or take effective contraceptive measures during the study and at least 70 days (10 weeks) after administration;
• Male subjects must agree to practice abstinence or use condoms as a contraceptive measure during the study and at least 70 days (10 weeks) after administration;
• 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 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 - 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;
• 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 study procedures.

Exclusion Criteria:

• Those with symptoms or medical history of cardiovascular, digestive, 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 study results;
• Pregnant or lactating women;
• Those whose blood pressure above 150/90 mmHg or below 85/55 mmHg (supine position);
• 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;
• Those who are HIV positive, syphilis positive, hepatitis B surface antigen positive, hepatitis C antibody positive, and/or with a positive drug urine test result;
• Those who have a history of alcohol or drug abuse in the past 10 years; Those with an allergic constitution, a history of allergic diseases or a history of drug allergy;
• 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;
• Those who have taken any drug that changes the activity of liver enzymes within 28 days before taking the investigational product or during the study;
• Those who have donated blood within 3 months before enrollment;
• Those who have participated in any clinical studies within 3 months before enrollment;
• Those who are the staff of the study site directly affiliated to this study or are their immediate family members. Immediate family members are defined as spouses, parents, children or siblings, whether related by blood or legally adopted;
• Those who are employees of TenNor Therapeutics;
• Other circumstances deemed by the investigator to be unsuitable for the subject to participate in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; The Placebo will be administered once in each group.
Experimental: TNP-2092 capsules 100mg	Drug: TNP-2092; The drug will be administered once in each group.; Other Names: Rifaquizinone; Drug: Placebo; The Placebo will be administered once in each group.
Experimental: TNP-2092 capsules 200mg	Drug: TNP-2092; The drug will be administered once in each group.; Other Names: Rifaquizinone; Drug: Placebo; The Placebo will be administered once in each group.
Experimental: TNP-2092 capsules 400mg (Food effect study Group A); After completed the single ascending dose study, the participant will convert to the food effect study. The drugs will be administered in the fasting state and in the fed state for two cycles, with a wash-out period of 4 days.	Drug: TNP-2092; The drug will be administered once in each group.; Other Names: Rifaquizinone; Drug: Placebo; The Placebo will be administered once in each group.
Experimental: TNP-2092 capsules 800mg	Drug: TNP-2092; The drug will be administered once in each group.; Other Names: Rifaquizinone; Drug: Placebo; The Placebo will be administered once in each group.
Experimental: TNP-2092 capsules 1200mg	Drug: TNP-2092; The drug will be administered once in each group.; Other Names: Rifaquizinone; Drug: Placebo; The Placebo will be administered once in each group.
Experimental: Food effect study Group B (TNP-2092 capsules 400 mg); The drugs will be administered in the fasting state and in the fed state for two cycles, with a wash-out period of 4 days.	Drug: TNP-2092; The drug will be administered once in each group.; Other Names: Rifaquizinone; Drug: Placebo; The Placebo will be administered once in each group.

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
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)	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	Before the first (Day1) administration (within 15 minutes), and 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 hours (h) after administration
Area Under the Plasma Concentration Versus Time Curve from 0 to the Last Measurable Concentration (AUC0-t)	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.	Before the first (Day1) administration (within 15 minutes), and 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 hours (h) after administration
Maximum Observed Plasma Concentration (Cmax) of TNP-2092	Plasma concentrations of TNP-2092 were measured by a specific and validated assay at specified time points	Before the first (Day1) administration (within 15 minutes), and 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 36 h, 48 h and 72 hours (h) after administration

Collaborators and Investigators

• Sponsor: TenNor Therapeutics (Suzhou) Limited

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2016
• Primary Completion (Actual): July 30, 2016
• Study Completion (Actual): July 30, 2016

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 20, 2023
• First Posted (Actual): December 21, 2023

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hyperammonemia
• Other Study ID Numbers: TNP-2092-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No