Clinical trial NCT05750355: Evaluate the Effect of TPN171H on the QT/QTc Interval in Healthy Volunteers
Official title: A Single-dose-oral, Ascending-Dose, Single-Center,Randomized, Double-Blind, Placebo-Parallel-controlled Study for the Evaluation of the Effect of TPN171H Tablets on the QT/QTc Intervals in Adult Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: TPN171H tablets
QT/QTc Intervals
Lead sponsor: Vigonvita Life Sciences
Sponsor class: INDUSTRY
First posted: 2023-03-01
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a single-dose orally administered, dose-escalation, single-center, randomized, double-blind, placebo-parallel controlled clinical study evaluating the effect of TPN171H tablets on QT/QTc interval in healthy subjects.The main objective was to evaluate the effect of TPN171H tablets on QT/QTc interval in healthy Chinese subjects after a single oral administration.

Detailed description: This trial was a single-center, randomized, double-blind, placebo parallel controlled trial of TPN171H tablets with single oral administration, dose escalation, in healthy Chinese subjects.

This trial plans to set up 4 dose groups, and a total of 32 healthy adult subjects are expected to be enrolled. All subjects will receive a single oral dose under fasting state, and complete 3 days of PK blood sampling, 12-lead ECG examination and other safety checks. The trial was sequential according to the principle of dose escalation, that is, the next dose group was tested on the premise that the safety and tolerability of the previous group were good.

Eligibility criteria: Inclusion Criteria:

1. Age 18-45 years old, both male and female;
2. Weight: male ≥ 50 kg, female ≥ 45 kg, 19 kg/m2 ≤ BMI ≤26 kg/m2
3. Three 12-lead ECG examinations (the average of three measurements will be used to determine eligibility), QTcF≤450 ms, PR interval ≤200 ms, and QRS duration \<120 ms;
4. Reliable contraceptive measures will be taken from the signing of the informed consent to 3 months after the medication, and there is no plan to donate sperm or eggs. The specific contraceptive measures are detailed in the appendix.
5. Able to understand the procedures and methods of this trial, willing to strictly abide by the clinical trial protocol to complete this trial, and voluntarily sign the informed consent.

Exclusion Criteria:

1. Known allergic history to the investigational drug and any of its components or related preparations;
2. People with allergic diseases, food allergies or allergic constitutions;
3. have a history of risk factors for torsdos de pointes, or have a family history of short QT syndrome, long QT syndrome, unexplained sudden death in young adulthood (≤40 years old), drowning or sudden infant death syndrome in first-degree relatives (i.e., biological parents, siblings or children);
4. Previous history of hyperkalemia, hypokalemia, hypermagnesemia, hypomagnesemia, hypercalcemia or hypocalcemia;
5. Those who have definite diseases of the central nervous system, cardiovascular system, digestive system (including those with moderate or severe fatty liver on B-ultrasound examination), respiratory system, urinary system, blood system, and metabolic disorders that require medical intervention or other diseases that are not suitable for clinical trials (such as psychiatric history, etc.);
6. Patients with blurred vision or history of ophthalmology (such as abnormal color vision, retinitis pigmentosa, macular degeneration);
7. Patients with a history of postural hypotension;
8. Patients with a history of acute respiratory infection or acute illness within 14 days before screening;
9. Those who had donated blood or lost ≥400 mL of blood within 3 months before screening;
10. Use of any drugs that inhibit or induce liver metabolism of drugs (such as: inducers - barbiturates, carbazepine, phenytoin, glucocorticoids, omeprazole; Inhibitors -SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazole, sedatives and hypnotics, verapamil, fluoroquinolones, antihistamines);
11. Those who have taken any prescription drugs, non-prescription drugs, health care products, vitamins and Chinese herbal medicines within 14 days before screening;
12. Consuming grapefruit, grapefruit, pitaya, mango and other fruits or related products that affect metabolic enzymes within 7 days before screening;
13. Intake of caffeine-rich or xanthine-rich beverages or foods (such as coffee, strong tea, chocolate, cola, etc.) within 48 h before screening;
14. Those who participated in other drug clinical trials within 3 months before screening;
15. Current or former drug users or alcohol addicts, current or former alcoholics (drinking more than 14 standard units per week). 1 standard unit containing 14g of alcohol (e.g. 360 mL beer or 45 mL spirits with 40% alcohol or 150 mL wine), or a positive breath test for alcohol;
16. Those who smoked more than 10 cigarettes per day in the previous 3 months were screened;
17. Physical examination, abnormal vital signs (ear temperature \>37.5℃, respiratory rate \>20 beats/minute, pulse rate \>100 beats/minute, systolic blood pressure ≥140 mmHg or \<90 mmHg, diastolic blood pressure ≥90 mmHg or \<50 mmHg), abnormal and clinically significant laboratory results, and those who have an impact on the evaluation of this trial;
18. Laboratory tests showed that serum potassium, magnesium and calcium were beyond the normal range and the abnormalities were judged by the researchers to be clinically significant;
19. Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, syphilis antibody (TPPA) or human immunodeficiency virus (HIV) antibody positive;
20. Abnormal chest X-ray (anteroposterior and lateral view) or lung CT results with clinical significance;
21. Women with positive blood pregnancy test (applicable to women) or lactating women;
22. Those who have other factors that the investigator considers unsuitable for participation in the trial.

Primary outcomes:
measure: QT Interval Corrected Using Fridericia's Formula
timeFrame: From Day 1 to Day3
Secondary outcomes:
measure: QT Interval
timeFrame: From Day 1 to Day3
measure: Corrected QT interval
timeFrame: From Day 1 to Day3
measure: PR interval
timeFrame: From Day 1 to Day3
measure: RR interval
timeFrame: From Day 1 to Day3
measure: QRS duration
timeFrame: From Day 1 to Day3
measure: Heart rate
timeFrame: From Day 1 to Day3
measure: T-wave
timeFrame: From Day 1 to Day3
measure: U-wave
timeFrame: From Day 1 to Day3
measure: Number of participants with arrhythmic
timeFrame: From Day 1 to Day3
measure: Tmax
timeFrame: From Day 1 to Day3
measure: Cmax
timeFrame: From Day 1 to Day3
measure: plasma half-life（T1/2）
timeFrame: From Day 1 to Day3
measure: Area under concentration-time curve (AUC0-t)
timeFrame: From Day 1 to Day3
measure: Incidence of adverse events
timeFrame: From Day 1 to Day3
measure: Severity of adverse events
timeFrame: From Day 1 to Day3
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital affiliated to Fudan University
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Jing Zhang
role: PRINCIPAL_INVESTIGATOR
References: