Clinical trial NCT06178718: A Phase 1 Study to Evaluate PK Profile and Food Effects on PK Parameters of TNP-2092 Capsules
Official title: A Phase 1 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperammonemia
Lead sponsor: TenNor Therapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: The First Hospital of Jilin University
First posted: 2023-12-21
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The aim of the study was to evaluate the tolerability and pharmacokinetic characteristics of TNP-2092 Capsules after single-dose administration in healthy subjects, and the food effect on pharmacokinetics.

Detailed description: This was a single-center, randomized, double-blind, placebo-controlled, dose-ascending single-dose-administration study, and a study on the food effects on pharmacokinetics. Five dose groups of 100 mg, 200 mg, 400 mg, 800 mg, and 1200 mg will be set up.

The 100 mg, 200 mg, 800 mg, and 1200 mg groups will complete the single ascending dose study, with 10 subjects randomized in each group, 8 subjects receiving TNP-2092 and 2 receiving placebo. The drug will be administered once in each group in the fasting state, and tolerability will be evaluated on D4. Subjects were sequentially enrolled into different dose groups in ascending order of dose, and only when the previous lower dose was confirmed to be safe and well tolerated could they be enrolled into the next higher dose group.

The 400 mg group will complete the single ascending dose study, food effect study and undergo the metabolic transformation evaluation. A total of 18 subjects will be enrolled in the group and randomized into Group A and Group B, with 8 subjects receiving the investigational product and 1 receiving placebo. 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. In terms of the administration sequence, Group A will first take TNP-2092 Capsules or placebo in the fasting state, and then TNP-2092 Capsules or placebo in the fed state; Group B will first take TNP-2092 Capsules or placebo in the fed state, and then TNP-2092 Capsules or placebo in the fasting state. Tolerability evaluation will be conducted on D4 and at the end of the study of food effects on pharmacokinetics (D8).

Eligibility criteria: 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 14 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.

Primary outcomes:
measure: Safety of TNP-2092 by Assessment of the Number of Participants With Adverse Events (AEs)
timeFrame: Up to 8 days after the first dosing.
measure: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) in Single Ascending Dose Study
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve From 0 to the Last Measurable Concentration (AUC0-last) in Single Ascending Dose Study
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of TNP-2092 in Single Ascending Dose Study
timeFrame: 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
measure: Time to Maximum Plasma Concentration (Tmax) of TNP-2092 in Single Ascending Dose Study
timeFrame: 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
measure: Terminal Elimination Half-life (T1/2) in Single Ascending Dose Study
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) in Food Effect Study
timeFrame: 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
measure: Area Under the Plasma Concentration Versus Time Curve From 0 to the Last Measurable Concentration (AUC0-last) in Food Effect Study
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of TNP-2092 in Food Effect Study
timeFrame: 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
measure: Time to Maximum Plasma Concentration (Tmax) of TNP-2092 in Food Effect Study
timeFrame: 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
measure: Terminal Elimination Half-life (T1/2) in Food Effect Study
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
Study officials:
affiliation: The First Hospital of Jilin University
name: Yanhua Ding, MD
role: PRINCIPAL_INVESTIGATOR
References: