Hyperammonemia
Conditions
Brief summary
The aim of this study was 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.
Detailed description
The aim of this study was 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. A total of 3 dose groups will be set up, i.e., 100 mg BID, 300 mg BID and 600 mg BID groups. Drugs will be orally administered 30 min after breakfast and dinner for 14 consecutive days, and last dose will be administered 30 min after breakfast on the morning of D15. Each dose group will include a study drug TNP-2092 capsule arm and a placebo control arm. Subjects will exit upon completion of the safety and tolerability evaluation on D17. Twelve liver cirrhosis patients with hyperammonemia are planned to be enrolled in each dose group. The 12 patients will be assigned in a ratio of 2:1 to the TNP-2092 capsule arm and the placebo arm, with 8 patients receiving TNP-2092 Capsules and 4 receiving placebos. Enrollment for the second dose group may start only after the previous dose group has fully completed the treatment period and passed the safety and tolerability evaluation.
Interventions
Administration orally.
DRUGPlacebo
Administration orally.
Sponsors
The First Hospital of Jilin University
TenNor Therapeutics (Suzhou) Limited
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65 (inclusive) years of age, male or female. * Clinically diagnosed with liver cirrhosis. * Fasting venous blood ammonia above upper limit of normal (ULN). * Organ functions must meet the following criteria: * Peripheral blood: absolute neutrophil count ≥ 0.5\*109/L, platelet ≥20\*109/L, hemoglobin ≥ 8 g/dL. * Liver: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN; serum total bilirubin (TBL) ≤ 5 × ULN. * Kidney: creatinine clearance ≥ 60 mL/min. * No malabsorption or other gastrointestinal disorders that affect drug absorption. * Weight ≥ 45 kg and body mass index \[BMI = weight (kg)/height 2 (m2) \] between 18 and 34 (inclusive) kg/m2. * Subjects (including their partners) will have no pregnancy plan and voluntarily take effective contraceptive measures within 6 months after drug withdrawal. Refer to Appendix 9 for specific contraceptive measures. * Subjects or their legal representatives sign the Informed Consent Form and fully understand the content, procedures, and potential adverse reactions prior to the initiation of the study. * Able to complete the study per the requirements in the study protocol.
Exclusion criteria
* Subjects who are allergic to rifamycin or quinolone antibacterial agents or those with an allergic constitution. * Pregnant or lactating women, or women of childbearing age with a positive pregnancy test from the screening period to initiation of the study treatment. * Subjects with serious nervous or mental disorders. * Subjects with Child-Pugh class C liver cirrhosis. * Subjects with Grade 2 or above hepatic encephalopathy. * Subjects who have been diagnosed with Clostridium difficile-induced pseudomembranous enteritis within 3 months. * Subjects who have had systemic infection or gastrointestinal bleeding within 7 days prior to screening. * Subjects with clinically significant abnormal clinical laboratory tests or other clinical findings indicative of clinically significant disorders that, in the opinion of the investigator, make them not eligible for this clinical study. * Subjects who have used sedatives, probiotics, cathartics or antibacterial agents within 7 days prior to screening. * Subjects who have used other study drugs or participated in other drug clinical trials within 1 month prior to screening. * Subjects need to use the following concomitant drugs during the study treatment period: cathartics and drugs for ammonia reduction listed in 5.2.1 in the Guidelines on the Management of Hepatic Encephalopathy in Liver Cirrhosis 2018 (e.g., lactulose, lactitol, L-ornithine L-aspartate(LOLA), rifaximin, other antibacterial agents, etc.) ; HIV protease inhibitors (e.g., ritonavir boosted or non-boosted saquinavir, atazanavir, darunavir, fosamprenavir, tipranavir, etc.) ; praziquantel; halothane; class IA and III antiarrhythmics (disopyramide, procainamide, quinidine, amiodarone, dofetilide, dronedarone, ibutilide, sotalol, etc.) ; strong inhibitors and inducers of liver metabolic enzymes; * Positive HIV antigen/antibody screen; positive Treponema pallidum antibody screen requires the investigator's judgment with the consideration of Rapid plasma regain（RPR） results. * Positive urine drug screen or history of drug abuse within the past 5 years. * Positive alcohol breath test. * Acute diseases or concomitant medications from screening to study medication. * Other circumstances deemed by the investigator to be unsuitable for enrollment in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accumulation Index Rac(AUC) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia | Day 1: 30-60 min prior to first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, and 12 h post-dose (prior to next dose). Day 15: 30-60 min pre-dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose. | 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. Rac (AUC) was calculated from the ratio of AUC0-tau (Day 15) to AUC0-tau(Day 1). |
| Time to Reach the Maximum Observed Plasma Concentration (Tmax) Day 15 | Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose | 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. |
| Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) Day 1 | Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose | 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. |
| Half Life (t1/2) of TNP-2092 Capsules on Day 1 | Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose | 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. |
| Half Life (t1/2) of TNP-2092 Capsules on Day 15 | Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose | 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. |
| Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 1 | Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose | 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. |
| Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 15 | Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose | 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. |
| Accumulation Index Rac(Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia | Day 1: 30-60 min prior to first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, and 12 h post-dose (prior to next dose). Day 15: 30-60 min pre-dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose. | 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. Rac (Cmax) was calculated from the ratio of Cmax (Day 15) to Cmax (Day 1) |
| Safety of TNP-2092 by Assessment of the Number of Participants With Adverse Events (AEs) | Up to 17 days after the first dosing. | To investigate the safety and tolerability of TNP-2092 by assessment of the number of participants with AEs following administration of TNP-2092 capsules. An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. |
| Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 1. | Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose | 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. |
| Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 1. | Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose | 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. |
| Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) on Day 15 | Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose | 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. |
| Time to Reach the Maximum Observed Plasma Concentration (Tmax) on Day 1 | Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose | 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. |
| Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 15. | Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose | 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. |
| Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 15. | Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Baseline, Day 7 and Day 15 | Evaluation of NCT-A is based on the time required to complete the test. The results will be positive according to following criteria: 1) the time is over 34.3 seconds while the age is less than 35 years; 2) the time is over 45.7 seconds while the age is between 35 to 44 years; 3) the time is over 52.8 seconds while age is between 45 to 54 years; 4) the time is over 61.9 seconds while the age is between 55 to 64 years. The positive result means a worse outcome. |
| Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Baseline, Day 7 and Day 15 | Evaluation of Digital symbol test (DST) is based on the score gained within 90 seconds, and the results are positive according to following criteria: 1) the score is less than 40.5 while the age is less than 35 years; 2) the score is less than 35.0 while the age is between 35 to 44 years; 3) the score is less than 28.5 while the age is between 45 to 54 years; 4) the score is less than 26.0 while the age is between 55 to 64 years. The positive result means a worse outcome. |
| Changes in the Total Scores of Quality of Life (QOL) From Baseline | Baseline, Day 7 and Day 15 | Changes in the total scores of QOL from baseline will be compared with the placebo to evaluate the preliminary efficacy of TNP-2092 Capsules in liver cirrhosis patients with hyperammonemia. The range of QOL scores is 30 \ 150. Patients with lower scores means a better outcome. |
| Proportion of Participants Whose Asterixis is Elicited | Baseline, Day 7 and Day 15 | Asterixis is a physical exam finding that can be elicited by asking the participant to extend the arms, flex the wrists, and spread the fingers wide. Clinically, asterixis produces flapping tremors. In a flapping tremor, an participant will flap their wrists like a bird flapping its wings. Asterixis elicited means a worse outcome. |
| Clinical Grade of Hepatic Encephalopathy | Baseline, Day 7 and Day 15 | Grade 0 of HE (without HE) is nomal, Grade 0 of HE (MHE) is alterations of brain function in neuropsychological or neurophysiological measures without clinical signs of HE, Grade 1 of HE is mild lack of awareness, Grade 2 of HE is lethargic, Grade 3 of HE is somnolent, and Grade 4 of HE is coma. Higher score means worse outcome. |
| Areas Under the Blood Ammonia Concentration-time Curve | Baseline to Day 15 | Plasma concentrations of Blood Ammonia were measured by a specific and validated assay. Changes in the Fasting Venous Blood Ammonia Concentration From Baseline were used to measure AUC. |
| Changes in the Fasting Venous Blood Ammonia Concentration From Baseline (Mean Pre-treatment Measured) | Baseline and Day 15 | The changes in the fasting venous blood ammonia concentration from baseline will be compared with the placebo to evaluate the preliminary efficacy of TNP-2092 Capsules in liver cirrhosis patients with hyperammonemia. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) TNP-2092 capsules: TNP-2092 capsules will be orally administered 30 min after breakfast and dinner for 14 consecutive days, and last dose will be administered 30 min after breakfast on the morning of D15. | 8 |
| TNP-2092 Capsules 300mg BID TNP-2092 capsules: TNP-2092 capsules will be orally administered 30 min after breakfast and dinner for 14 consecutive days, and last dose will be administered 30 min after breakfast on the morning of D15. | 8 |
| TNP-2092 Capsules 600mg BID TNP-2092 capsules: TNP-2092 capsules will be orally administered 30 min after breakfast and dinner for 14 consecutive days, and last dose will be administered 30 min after breakfast on the morning of D15. | 8 |
| TNP-2092 Capsules Placebo TNP-2092 capsules Placebo: TNP-2092 capsules Placebo will be orally administered 30 min after breakfast and dinner for 14 consecutive days, and last dose will be administered 30 min after breakfast on the morning of D15. | 12 |
| Total | 36 |
Baseline characteristics
| Characteristic | Total | TNP-2092 Capsules 100mg Twice Daily(BID) | TNP-2092 Capsules 300mg BID | TNP-2092 Capsules Placebo | TNP-2092 Capsules 600mg BID |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 8 Participants | 8 Participants | 12 Participants | 8 Participants |
| Age, Continuous | 51.1 years STANDARD_DEVIATION 8 | 49.5 years STANDARD_DEVIATION 7.19 | 50.4 years STANDARD_DEVIATION 5.71 | 52.3 years STANDARD_DEVIATION 10.15 | 51.9 years STANDARD_DEVIATION 7.97 |
| Fasting Venous Blood Ammonia Concentration | 94.0 μmol/L STANDARD_DEVIATION 32 | 90.1 μmol/L STANDARD_DEVIATION 27.1 | 80.3 μmol/L STANDARD_DEVIATION 19.5 | 115.8 μmol/L STANDARD_DEVIATION 39.1 | 78.8 μmol/L STANDARD_DEVIATION 17.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 36 Participants | 8 Participants | 8 Participants | 12 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 8 Participants | 0 Participants | 1 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 28 Participants | 8 Participants | 7 Participants | 8 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 12 |
| other Total, other adverse events | 6 / 8 | 6 / 8 | 7 / 8 | 8 / 12 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 1 / 12 |
Outcome results
Primary
Accumulation Index Rac(AUC) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia
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. Rac (AUC) was calculated from the ratio of AUC0-tau (Day 15) to AUC0-tau(Day 1).
Time frame: Day 1: 30-60 min prior to first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, and 12 h post-dose (prior to next dose). Day 15: 30-60 min pre-dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose.
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Accumulation Index Rac(AUC) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia | 1.09 ratio | Standard Deviation 0.4 |
| TNP-2092 Capsules 300mg BID | Accumulation Index Rac(AUC) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia | 1.38 ratio | Standard Deviation 0.39 |
| TNP-2092 Capsules 600mg BID | Accumulation Index Rac(AUC) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia | 1.47 ratio | Standard Deviation 0.55 |
Primary
Accumulation Index Rac(Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia
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. Rac (Cmax) was calculated from the ratio of Cmax (Day 15) to Cmax (Day 1)
Time frame: Day 1: 30-60 min prior to first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, and 12 h post-dose (prior to next dose). Day 15: 30-60 min pre-dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose.
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Accumulation Index Rac(Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia | 0.74 ratio | Standard Deviation 0.22 |
| TNP-2092 Capsules 300mg BID | Accumulation Index Rac(Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia | 1.23 ratio | Standard Deviation 0.49 |
| TNP-2092 Capsules 600mg BID | Accumulation Index Rac(Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia | 1.26 ratio | Standard Deviation 0.42 |
Primary
Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) Day 1
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.
Time frame: Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) Day 1 | 332 h*ng/ml | Standard Deviation 188 |
| TNP-2092 Capsules 300mg BID | Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) Day 1 | 561 h*ng/ml | Standard Deviation 565 |
| TNP-2092 Capsules 600mg BID | Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) Day 1 | 1790 h*ng/ml | Standard Deviation 1210 |
Primary
Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) on Day 15
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.
Time frame: Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) on Day 15 | 396 h*ng/ml | Standard Deviation 257 |
| TNP-2092 Capsules 300mg BID | Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) on Day 15 | 756 h*ng/ml | Standard Deviation 570 |
| TNP-2092 Capsules 600mg BID | Area Under the Plasma Concentration-time Curve From the Time of Administration Extrapolated to Infinity (AUC0-∞) on Day 15 | 2680 h*ng/ml | Standard Deviation 1790 |
Primary
Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 1.
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.
Time frame: Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 1. | 309 h*ng/ml | Standard Deviation 178 |
| TNP-2092 Capsules 300mg BID | Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 1. | 524 h*ng/ml | Standard Deviation 537 |
| TNP-2092 Capsules 600mg BID | Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 1. | 1610 h*ng/ml | Standard Deviation 1200 |
Primary
Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 15.
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.
Time frame: Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 15. | 380 h*ng/ml | Standard Deviation 247 |
| TNP-2092 Capsules 300mg BID | Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 15. | 739 h*ng/ml | Standard Deviation 555 |
| TNP-2092 Capsules 600mg BID | Area Under the Plasma Concentration-time Curve From the Time of Administration to the Time of the Last Measurable Plasma Concentration (AUC0-last) on Day 15. | 2610 h*ng/ml | Standard Deviation 1730 |
Primary
Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 1
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.
Time frame: Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 1 | 309 h*ng/mL | Standard Deviation 179 |
| TNP-2092 Capsules 300mg BID | Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 1 | 525 h*ng/mL | Standard Deviation 538 |
| TNP-2092 Capsules 600mg BID | Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 1 | 1610 h*ng/mL | Standard Deviation 1200 |
Primary
Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 15
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.
Time frame: Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 15 | 303 h*ng/mL | Standard Deviation 187 |
| TNP-2092 Capsules 300mg BID | Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 15 | 646 h*ng/mL | Standard Deviation 466 |
| TNP-2092 Capsules 600mg BID | Area Under the Plasma Concentration-time Curve Within a Dosing Interval (AUC0-tau) on Day 15 | 2230 h*ng/mL | Standard Deviation 1480 |
Primary
Half Life (t1/2) of TNP-2092 Capsules on Day 1
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.
Time frame: Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Half Life (t1/2) of TNP-2092 Capsules on Day 1 | 2.52 h | Standard Deviation 0.63 |
| TNP-2092 Capsules 300mg BID | Half Life (t1/2) of TNP-2092 Capsules on Day 1 | 2.23 h | Standard Deviation 0.81 |
| TNP-2092 Capsules 600mg BID | Half Life (t1/2) of TNP-2092 Capsules on Day 1 | 2.99 h | Standard Deviation 2.29 |
Primary
Half Life (t1/2) of TNP-2092 Capsules on Day 15
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.
Time frame: Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Half Life (t1/2) of TNP-2092 Capsules on Day 15 | 8.17 h | Standard Deviation 1.84 |
| TNP-2092 Capsules 300mg BID | Half Life (t1/2) of TNP-2092 Capsules on Day 15 | 6.92 h | Standard Deviation 2.63 |
| TNP-2092 Capsules 600mg BID | Half Life (t1/2) of TNP-2092 Capsules on Day 15 | 7.93 h | Standard Deviation 1.09 |
Primary
Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 1.
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.
Time frame: Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 1. | 90.4 ng/ml | Standard Deviation 42.9 |
| TNP-2092 Capsules 300mg BID | Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 1. | 140 ng/ml | Standard Deviation 120 |
| TNP-2092 Capsules 600mg BID | Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 1. | 415 ng/ml | Standard Deviation 294 |
Primary
Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 15.
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.
Time frame: Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 15. | 60.8 ng/ml | Standard Deviation 28.5 |
| TNP-2092 Capsules 300mg BID | Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 15. | 164 ng/ml | Standard Deviation 118 |
| TNP-2092 Capsules 600mg BID | Maximum Observed Plasma Concentration (Cmax) of TNP-2092 Capsules in Liver Cirrhosis Patients With Hyperammonemia on Day 15. | 543 ng/ml | Standard Deviation 420 |
Primary
Safety of TNP-2092 by Assessment of the Number of Participants With Adverse Events (AEs)
To investigate the safety and tolerability of TNP-2092 by assessment of the number of participants with AEs following administration of TNP-2092 capsules. An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 17 days after the first dosing.
Population: All subjects who have received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Safety of TNP-2092 by Assessment of the Number of Participants With Adverse Events (AEs) | 6 participants |
| TNP-2092 Capsules 300mg BID | Safety of TNP-2092 by Assessment of the Number of Participants With Adverse Events (AEs) | 6 participants |
| TNP-2092 Capsules 600mg BID | Safety of TNP-2092 by Assessment of the Number of Participants With Adverse Events (AEs) | 7 participants |
| Placebo | Safety of TNP-2092 by Assessment of the Number of Participants With Adverse Events (AEs) | 8 participants |
Primary
Time to Reach the Maximum Observed Plasma Concentration (Tmax) Day 15
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.
Time frame: Day 15: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 24 h and 36 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Time to Reach the Maximum Observed Plasma Concentration (Tmax) Day 15 | 4.43 h | Standard Deviation 0.78 |
| TNP-2092 Capsules 300mg BID | Time to Reach the Maximum Observed Plasma Concentration (Tmax) Day 15 | 4.75 h | Standard Deviation 0.46 |
| TNP-2092 Capsules 600mg BID | Time to Reach the Maximum Observed Plasma Concentration (Tmax) Day 15 | 4.50 h | Standard Deviation 1.85 |
Primary
Time to Reach the Maximum Observed Plasma Concentration (Tmax) on Day 1
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.
Time frame: Day 1: 30-60 min prior to the first dose, and 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h and 12 h post-dose
Population: All subjects who have been randomized into groups, have received at least one dose of study drug, and have at least one evaluable pharmacokinetic parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Time to Reach the Maximum Observed Plasma Concentration (Tmax) on Day 1 | 4.75 h | Standard Deviation 0.46 |
| TNP-2092 Capsules 300mg BID | Time to Reach the Maximum Observed Plasma Concentration (Tmax) on Day 1 | 5.13 h | Standard Deviation 0.36 |
| TNP-2092 Capsules 600mg BID | Time to Reach the Maximum Observed Plasma Concentration (Tmax) on Day 1 | 5.13 h | Standard Deviation 0.35 |
Secondary
Areas Under the Blood Ammonia Concentration-time Curve
Plasma concentrations of Blood Ammonia were measured by a specific and validated assay. Changes in the Fasting Venous Blood Ammonia Concentration From Baseline were used to measure AUC.
Time frame: Baseline to Day 15
Population: All the subjects who were randomized into groups
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Areas Under the Blood Ammonia Concentration-time Curve | Day 1 | 481.6 h*μmol/L | Standard Deviation 564.5 |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Areas Under the Blood Ammonia Concentration-time Curve | Day 1-Day 15 | -1716.7 h*μmol/L | Standard Deviation 5778.5 |
| TNP-2092 Capsules 300mg BID | Areas Under the Blood Ammonia Concentration-time Curve | Day 1-Day 15 | -3205.4 h*μmol/L | Standard Deviation 8311.8 |
| TNP-2092 Capsules 300mg BID | Areas Under the Blood Ammonia Concentration-time Curve | Day 1 | 480.2 h*μmol/L | Standard Deviation 607.9 |
| TNP-2092 Capsules 600mg BID | Areas Under the Blood Ammonia Concentration-time Curve | Day 1 | 225.0 h*μmol/L | Standard Deviation 544.1 |
| TNP-2092 Capsules 600mg BID | Areas Under the Blood Ammonia Concentration-time Curve | Day 1-Day 15 | -5805.6 h*μmol/L | Standard Deviation 6080.5 |
| Placebo | Areas Under the Blood Ammonia Concentration-time Curve | Day 1 | 85.5 h*μmol/L | Standard Deviation 999.3 |
| Placebo | Areas Under the Blood Ammonia Concentration-time Curve | Day 1-Day 15 | -5476.3 h*μmol/L | Standard Deviation 12816.5 |
Secondary
Changes in the Fasting Venous Blood Ammonia Concentration From Baseline (Mean Pre-treatment Measured)
The changes in the fasting venous blood ammonia concentration from baseline will be compared with the placebo to evaluate the preliminary efficacy of TNP-2092 Capsules in liver cirrhosis patients with hyperammonemia.
Time frame: Baseline and Day 15
Population: All the subjects who were randomized into groups
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Changes in the Fasting Venous Blood Ammonia Concentration From Baseline (Mean Pre-treatment Measured) | 5.7 μmol/L | Standard Deviation 17.5 |
| TNP-2092 Capsules 300mg BID | Changes in the Fasting Venous Blood Ammonia Concentration From Baseline (Mean Pre-treatment Measured) | -2.1 μmol/L | Standard Deviation 22.49 |
| TNP-2092 Capsules 600mg BID | Changes in the Fasting Venous Blood Ammonia Concentration From Baseline (Mean Pre-treatment Measured) | -14.1 μmol/L | Standard Deviation 18.12 |
| Placebo | Changes in the Fasting Venous Blood Ammonia Concentration From Baseline (Mean Pre-treatment Measured) | 0.5 μmol/L | Standard Deviation 45.29 |
Secondary
Changes in the Total Scores of Quality of Life (QOL) From Baseline
Changes in the total scores of QOL from baseline will be compared with the placebo to evaluate the preliminary efficacy of TNP-2092 Capsules in liver cirrhosis patients with hyperammonemia. The range of QOL scores is 30 \ 150. Patients with lower scores means a better outcome.
Time frame: Baseline, Day 7 and Day 15
Population: All the subjects who were randomized into groups
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Changes in the Total Scores of Quality of Life (QOL) From Baseline | Day 7 | -6.1 score on a scale | Standard Deviation 5.64 |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Changes in the Total Scores of Quality of Life (QOL) From Baseline | Day 15 | -3.0 score on a scale | Standard Deviation 4.73 |
| TNP-2092 Capsules 300mg BID | Changes in the Total Scores of Quality of Life (QOL) From Baseline | Day 15 | 7.1 score on a scale | Standard Deviation 15.82 |
| TNP-2092 Capsules 300mg BID | Changes in the Total Scores of Quality of Life (QOL) From Baseline | Day 7 | 6.4 score on a scale | Standard Deviation 15.8 |
| TNP-2092 Capsules 600mg BID | Changes in the Total Scores of Quality of Life (QOL) From Baseline | Day 15 | 4.6 score on a scale | Standard Deviation 5.63 |
| TNP-2092 Capsules 600mg BID | Changes in the Total Scores of Quality of Life (QOL) From Baseline | Day 7 | 3.1 score on a scale | Standard Deviation 13.91 |
| Placebo | Changes in the Total Scores of Quality of Life (QOL) From Baseline | Day 7 | 0.5 score on a scale | Standard Deviation 9.21 |
| Placebo | Changes in the Total Scores of Quality of Life (QOL) From Baseline | Day 15 | -1.4 score on a scale | Standard Deviation 15.88 |
Secondary
Clinical Grade of Hepatic Encephalopathy
Grade 0 of HE (without HE) is nomal, Grade 0 of HE (MHE) is alterations of brain function in neuropsychological or neurophysiological measures without clinical signs of HE, Grade 1 of HE is mild lack of awareness, Grade 2 of HE is lethargic, Grade 3 of HE is somnolent, and Grade 4 of HE is coma. Higher score means worse outcome.
Time frame: Baseline, Day 7 and Day 15
Population: All the subjects who were randomized into groups
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 2 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 1 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 4 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 0 of HE (MHE) | 6 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 0 of HE (MHE) | 7 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 0 of HE (without HE) | 1 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 0 of HE (without HE) | 2 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 2 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 1 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 1 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 0 of HE (MHE) | 7 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 0 of HE (without HE) | 1 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 2 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 4 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 4 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 3 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 3 of HE | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 3 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 0 of HE (without HE) | 2 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 0 of HE (MHE) | 6 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 1 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 2 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 3 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 4 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 0 of HE (without HE) | 1 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 0 of HE (MHE) | 7 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 1 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 2 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 3 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 4 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 0 of HE (without HE) | 1 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 0 of HE (MHE) | 7 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 1 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 2 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 3 of HE | 0 Participants |
| TNP-2092 Capsules 300mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 4 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 3 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 2 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 3 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 2 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 4 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 4 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 3 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 0 of HE (without HE) | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 1 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 0 of HE (MHE) | 8 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 0 of HE (without HE) | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 1 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 0 of HE (MHE) | 8 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 0 of HE (without HE) | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 4 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 0 of HE (MHE) | 8 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 2 of HE | 0 Participants |
| TNP-2092 Capsules 600mg BID | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 1 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 0 of HE (without HE) | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 2 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 0 of HE (MHE) | 12 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 2 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 2 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 0 of HE (without HE) | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 0 of HE (MHE) | 12 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 3 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 3 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 4 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 1 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 4 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 1 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Baseline | Grade 4 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 1 of HE | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 0 of HE (without HE) | 0 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 7 | Grade 0 of HE (MHE) | 12 Participants |
| Placebo | Clinical Grade of Hepatic Encephalopathy | Day 15 | Grade 3 of HE | 0 Participants |
Secondary
Proportion of Participants Whose Asterixis is Elicited
Asterixis is a physical exam finding that can be elicited by asking the participant to extend the arms, flex the wrists, and spread the fingers wide. Clinically, asterixis produces flapping tremors. In a flapping tremor, an participant will flap their wrists like a bird flapping its wings. Asterixis elicited means a worse outcome.
Time frame: Baseline, Day 7 and Day 15
Population: All the subjects who were randomized into groups
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited at Baseline | Yes | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited at Baseline | No | 8 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 7 | Yes | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 7 | No | 8 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 15 | Yes | 0 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 15 | No | 8 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 15 | No | 8 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 7 | No | 8 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited at Baseline | Yes | 0 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 7 | Yes | 0 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited at Baseline | No | 8 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 15 | Yes | 0 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited at Baseline | No | 8 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 7 | Yes | 0 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 7 | No | 8 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 15 | No | 8 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 15 | Yes | 0 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited at Baseline | Yes | 0 Participants |
| Placebo | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 15 | Yes | 0 Participants |
| Placebo | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 15 | No | 12 Participants |
| Placebo | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited at Baseline | No | 12 Participants |
| Placebo | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 7 | No | 12 Participants |
| Placebo | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited at Baseline | Yes | 0 Participants |
| Placebo | Proportion of Participants Whose Asterixis is Elicited | Whether asterixis is elicited on Day 7 | Yes | 0 Participants |
Secondary
Proportion of Participants With Positive Result of Digital Symbol Test (DST)
Evaluation of Digital symbol test (DST) is based on the score gained within 90 seconds, and the results are positive according to following criteria: 1) the score is less than 40.5 while the age is less than 35 years; 2) the score is less than 35.0 while the age is between 35 to 44 years; 3) the score is less than 28.5 while the age is between 45 to 54 years; 4) the score is less than 26.0 while the age is between 55 to 64 years. The positive result means a worse outcome.
Time frame: Baseline, Day 7 and Day 15
Population: All the subjects who were randomized into groups
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Baseline | 4 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Day 7 | 4 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Day 15 | 0 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Day 7 | 2 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Baseline | 2 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Day 15 | 1 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Baseline | 3 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Day 7 | 3 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Day 15 | 3 Participants |
| Placebo | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Day 7 | 8 Participants |
| Placebo | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Day 15 | 7 Participants |
| Placebo | Proportion of Participants With Positive Result of Digital Symbol Test (DST) | Baseline | 7 Participants |
Secondary
Proportion of Participants With Positive Result of Number Connection Test A (NCT-A)
Evaluation of NCT-A is based on the time required to complete the test. The results will be positive according to following criteria: 1) the time is over 34.3 seconds while the age is less than 35 years; 2) the time is over 45.7 seconds while the age is between 35 to 44 years; 3) the time is over 52.8 seconds while age is between 45 to 54 years; 4) the time is over 61.9 seconds while the age is between 55 to 64 years. The positive result means a worse outcome.
Time frame: Baseline, Day 7 and Day 15
Population: All the subjects who were randomized into groups
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Baseline | 6 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Day 15 | 5 Participants |
| TNP-2092 Capsules 100mg Twice Daily(BID) | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Day 7 | 7 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Baseline | 6 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Day 15 | 7 Participants |
| TNP-2092 Capsules 300mg BID | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Day 7 | 6 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Day 7 | 8 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Baseline | 8 Participants |
| TNP-2092 Capsules 600mg BID | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Day 15 | 8 Participants |
| Placebo | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Baseline | 12 Participants |
| Placebo | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Day 15 | 11 Participants |
| Placebo | Proportion of Participants With Positive Result of Number Connection Test A (NCT-A) | Day 7 | 12 Participants |