Study of the Pharmacokinetics and Safety of TPN171H Tablets in Subjects With Mild ,Moderate Hepatic Insufficiency and Normal Liver Function

A Phase I Clinical Study of the Pharmacokinetics and Safety of TPN171H Tablets in Subjects With Mild Liver Insufficiency, Moderate Liver Insufficiency and Normal Liver Function

The study aims to investigate and compare the effect of TPN171H on subjects with mild and moderate hepatic impairment compared to healthy subjects.

Study Overview

• Status: Completed
• Conditions: Erectile Dysfunction; Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: TPN171H

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Hepatic Insufficiency Participants：

1. Signing the informed consent forms；
2. Take proper contraceptive during the study and within 6 months after the study completed;
3. 18 years to 65 years (inclusive)；
4. Male≥50kg，femal≥45kg, Body mass index should be between 18 and 30 kg/m2 (inclusive)；
5. No medication was used before screening，or stable medication for 4 weeks. Liver cirrhosis；
6. Child-Pugh class A or Child-Pugh class B, liver function impairment caused by previous primary liver disease (drug-induced liver injury was excluded)；
7. The clinical diagnosis was liver cirrhosis.

Normal liver function Participants：

1. Signing the informed consent forms；
2. Take proper contraceptive during the study and within 6 months after the study completed;
3. 18 years to 65 years (inclusive)；
4. Male≥50kg，femal≥45kg, Body mass index should be between 18 and 30 kg/m2 (inclusive)；
5. No medication was used before screening；
6. Clinical laboratory tests during the screening period were normal，or the abnormality has no clinical significance.

Exclusion Criteria:

1. Allergic constitution；
2. Patients who have a history of NAION, or with a known genetically degenerative retinopathy, including retinitis pigmentosa；
3. Patients with alcohol addiction or persistent abuse of drugs of dependence;
4. Smoking more than 5 cigarettes per day within 3 months prior to screening；
5. Drug abuse within 3 months prior to screening，or the long-term use of benzodiazepine medications；
6. Blood donation (or blood loss) ≥200mL, or receiving whole blood transfusions or erythrocyte suspension transfusions within 3 months prior to the screening；
7. Patients with severe or clinically significant infections, traumas, and major trauma surgery within 4 weeks before screening;
8. Participated in any other intervention clinical trial within 1 months before screening；
9. Within 28 days before screening, inhibitors or inducers of CYP3A4 were used；
10. have a scheduled surgical plan during the study period;
11. Patients with clinically significant ECG abnormalities；
12. Creatinine clearance <60ml/min;
13. A pregnant/lactating woman, or has a positive pregnancy test at screening or during the trial；
14. Screening positive for viral hepatitis (including hepatitis B and C), HIV or syphilis (normal liver function only) ；
15. Urine drug screening positive；

16. Any factors that the investigator considers inappropriate for participation in the study；

    Additional exclusion criteria for subjects with hepatic insufficiency (those who meet any of the followings are ineligible):

17. History of liver transplant;
18. History of any serious diseases, other than primary liver diseases, or history of disorders and/or clinically significant abnormal laboratory findings that, as judged by the investigator, may affect the results of the study, including but not limited to the history of diseases in the circulatory system, endocrine system, nervous system, digestive system, urinary system or blood, immune, mental and metabolic diseases;
19. Subjects with liver failure, acute liver injury ,or subjects with cirrhosis complicated with hepatocellular carcinoma or symptomatic hepatic encephalopathy, etc., are deemed as unsuitable for this study by the investigator；
20. ALT or AST >10*ULN，NE#<0.75*10^9/L,HGB<60g/L，AFP >100ng/ml；
21. Positive for HIV antibody screening; a rapid plasma reagin (RPR) test is required for a subject who tests positive for syphilis antibodies, and the subject should be excluded if the RPR result is also positive.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mild hepatic impairment; Subjects with mild hepatic impairment	Drug: TPN171H; 10 mg TPN171H tablets，single dose
Experimental: moderate hepatic impairment; Subjects with mild moderate impairment	Drug: TPN171H; 10 mg TPN171H tablets，single dose
Experimental: healthy volunteers; Subjects with normal hepatic function	Drug: TPN171H; 10 mg TPN171H tablets，single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve from single dosing time extrapolated to infinity（AUC0-∞）	Area under the plasma concentration versus time curve from single dosing time extrapolated to infinity（AUC0-∞） will be compared between normal hepatic function patients and mild or moderate hepatic dysfunction patients	72 hours after dosing
Area under the plasma concentration versus time curve from the last time of dosing to the last measurable concentration （AUC0-t）	Area under the plasma concentration versus time curve from the last time of dosing to the last measurable concentration （AUC0-t） will be compared between normal hepatic function patients and mild or moderate hepatic dysfunction patients	72 hours after dosing
Maximum Plasma Concentration (Cmax)	Maximum Plasma Concentration (Cmax) will be compared between normal hepatic function patients and mild or moderate hepatic dysfunction patients	72 hours after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of Participants With Adverse Events and Serious Adverse Events	From administration of study drug through 7 days after administration of study drug

Collaborators and Investigators

• Sponsor: Vigonvita Life Sciences
• Collaborators: Shanghai Institute of Materia Medica, Chinese Academy of Sciences
• Investigators: Study Chair: Yan Hua Ding, MD, The First Affiliated Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Actual): February 6, 2022
• Study Completion (Actual): February 6, 2022

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: December 22, 2021
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Hypertension, Pulmonary; Hypertension; Erectile Dysfunction; Pulmonary Arterial Hypertension
• Other Study ID Numbers: TPN171H-09

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