Tolerance, PK and PD Effects Study of TPN-672 in Chinese Healthy Volunteers

Study Overview
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Brief Summary
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This is a single-site, randomized, double-blind, placebo-controlled, incremental phase I clinical trial to evaluate preliminarily the tolerance, pharmacokinetics and pharmacodynamic effects of TPN672 maleate in Chinese healthy volunteers after single dose administration.

Official Title
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A Single Site, Randomized, Double-blind, Placebo-controlled, Incremental Phase I Clinical Trial: to Evaluate the Tolerance, PK and PD Effects of TPN-672 Maleate in Chinese Healthy Volunteers After Single Dose Administration.

Conditions
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PHA1A

Intervention / Treatment
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* Drug: TPN-672


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight > 50kg(male) or > 45kg(female), 19 <BMI<26 kg/m2. Good communication with investigators, willingness and ability to abide by the lifestyle restrictions stipulated in clinical trial Women or men within childbearing age do not have a fertility plan within 3 months after the end of the trial, and agree to adopt contraceptive measures approved (such as intrauterine device, condom, sperm killing gel, condom, uterine cap, etc.) throughout the clinical trial period. Fully understand the purpose and requirements of the trial, voluntarily participate in the clinical trial and sign the written informed consent, can complete the entire trial process according to the requirements of the trial. Exclusion Criteria: Investigator determined that there were diseases or functional disorders affecting clinical trials, including, but not limited to, central nervous system, cardiovascular system, respiratory system, digestive system, urinary system, endocrine system and blood system. Mental illness or previous history of mental illness; Have a history of ophthalmic diseases, such as abnormal color vision, retinitis pigmentosa, macular degeneration, etc. Have a history of malignant tumors or other diseases that are not suitable for clinical trials; Any surgical condition or condition that may significantly affect drug absorption, distribution, metabolism and excretion, or that may pose a hazard to the subjects participating in the study, such as history of gastrointestinal surgery (gastrectomy, gastrointestinal anastomosis, intestinal resection, etc.), urinary tract obstruction or dysuria, gastroenteritis, gastrointestinal ulcer, gastrointestinal bleeding, etc. Those who are known to have a history of drug allergy, allergic disease or allergic constitution of the tested drug ingredients or similar drugs; Smokers who smoked more than 10 cigarettes or the same amount of tobacco per day in the first year of screening; Alcohol addiction within 1 year before screening, with an average weekly alcohol intake of more than 14 units (1 unit = 285 ml beer or 25 ml spirits or 150 ml wine) or positive alcohol breath test; Those who had a history of drug abuse or drug abuse within 1 year before screening, or those who had positive urinary drug screening; Physical examination, current medical history and vital signs were found to be abnormal by researchers and have clinical significance. Resting pulse rate < 55/min or > 100/min; systolic pressure < 90 mmHg or > 140 mmHg, diastolic pressure < 60 mmHg or > 90 mmHg; 12-lead electrocardiogram (ECG) examination was found to be abnormal by investigator and had clinical significance; or the following ECG abnormalities occurred: PR interval > 220 ms, QRS complex wave duration > 120 ms, long QT syndrome (QTc > 450 ms); Family history of sudden cardiac death (less than 40 years old); Abnormal blood routine examination and urine routine examination have clinical significance. Aspartate transferase (AST), alanine transferase (ALT), creatinine (Cr), urea nitrogen (BUN) exceeded the normal upper limit. HBsAg, HCV-Ab, HIV-Ab and TRUST positive patients; Pregnant or lactating women or male subjects whose spouses have child-rearing plans within three months; Those who took any medicine within 2 weeks before admission, including prescription and non-prescription drugs; Blood donation or blood loss (> 200 ml) within 3 months before admission, or a history of using blood products; Participated in any clinical trials within 3 months before admission; Those who had a history of operation within 3 months before admission, or who had not recovered from the operation, or who had anticipated operation plan during the trial period; Do not agree to abide by the following conditions during the experiment: prohibit the use of tobacco, alcohol or caffeine-containing beverages, avoid strenuous exercise; Personnel directly related to this clinical trial; Investigator believes that other subjects are not suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.125mg single dose<br>single dose of TPN-672 0.125mg, 2 subjects | Drug: TPN-672<br>* single dose of TPN-672 maleate tablet<br>* Other names: TPN-672 maleate tablet;|
| Experimental: 0.25mg single dose<br>single dose of 0.25mg, 10 subjects (8 for TPN-672, 2 for placebo) | Drug: TPN-672<br>* single dose of TPN-672 maleate tablet<br>* Other names: TPN-672 maleate tablet;|
| Experimental: 0.5mg single dose<br>single dose of 0.5mg, 10 subjects (8 for TPN-672, 2 for placebo) | Drug: TPN-672<br>* single dose of TPN-672 maleate tablet<br>* Other names: TPN-672 maleate tablet;|
| Experimental: 1mg single dose<br>single dose of 1mg, 10 subjects (8 for TPN-672, 2 for placebo) | Drug: TPN-672<br>* single dose of TPN-672 maleate tablet<br>* Other names: TPN-672 maleate tablet;|
| Experimental: 2mg single dose<br>single dose of 2mg, 10 subjects (8 for TPN-672, 2 for placebo) | Drug: TPN-672<br>* single dose of TPN-672 maleate tablet<br>* Other names: TPN-672 maleate tablet;|
| Experimental: 3mg single dose<br>single dose of 3mg, 10 subjects (8 for TPN-672, 2 for placebo) | Drug: TPN-672<br>* single dose of TPN-672 maleate tablet<br>* Other names: TPN-672 maleate tablet;|
| Experimental: 4mg single dose<br>single dose of 4mg, 10 subjects (8 for TPN-672, 2 for placebo) | Drug: TPN-672<br>* single dose of TPN-672 maleate tablet<br>* Other names: TPN-672 maleate tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Number of Subjects with adverse events during clinical trial | 48 hours | 
| Cmax | Maximum Plasma Concentration | 48 hours | 
| AUC | Area Under the Curve | 48 hours | 
| Tmax | Time to Cmax | 48 hours | 
| T1/2 | Time of half life | 48 hours | 
| ACR | Apparent Clearance Rate | 48 hours | 
| ADV | Apparent Distribution Volume | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| prolactin | serum prolactin test | 48 hours | 
| temperature | ear temperature | 48 hours | 
| pulse rate | pulse rate | 48 hours | 
| respiratory | frequency of respiratory per minute | 48 hours | 
| blood pressure | lying blood pressure， systolic and diastolic | 48 hours | 
| electrocardiogram(ECG) | the number of subjects with abnormal ECG report by 12-lead electrocardiogram | 48 hours | 
| QTc | QTc interval | 48 hours | 
| Extrapyramidal symptoms | Simpson Angus Rating Scale (SAS), total score ranges from 0 to 40, of which lower values represent a better outcome. | 48 hours | 
| Involuntary Movement | Abnormal Involuntary Movement Scale (AIMS), total score ranges from 0 to 14, of which lower values represent a better outcome. | 48 hours | 
| Akathisia | Barnes Akathisia Rating Scale (BARS), total score ranges from 0 to 40, of which lower values represent a better outcome. | 48 hours | 
| IL-6 | Serum concentration of Interleukin-6 | 48 hours | 
| IL-4 | Serum concentration of Interleukin-4 | 48 hours | 
| IL-1 | Serum concentration of Interleukin-1 | 48 hours | 
| IL-2 | Serum concentration of Interleukin-2 | 48 hours | 
| INF-gamma | Serum concentration of Interferon-gamma | 48 hours | 
| TNF-alpha | Serum concentration of Tumor necrosis factor-alpha | 48 hours | 
| 5-HT | Serum concentration of serotonin | 48 hours | 
| DA | Serum concentration of Dopamine | 48 hours | 
| NE | Serum concentration of Norepinephrine | 48 hours | 
| BDNF | Serum concentration of Brain-derived neurotrophic factor | 48 hours | 
| Glutamic acid | Serum concentration of Glutamic acid | 48 hours | 
| GABA | Serum concentration of gamma-aminobutyric acid | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tolerance, pharmacokinetics, pharmacodynamics, TPN-672