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

Early Phase 1
Conditions
PHA1A
Interventions
Registration Number
NCT03931668
Lead Sponsor
Shanghai Mental Health Center
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
62
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
0.125mg single doseTPN-672single dose of TPN-672 0.125mg, 2 subjects
0.25mg single doseTPN-672single dose of 0.25mg, 10 subjects (8 for TPN-672, 2 for placebo)
0.5mg single doseTPN-672single dose of 0.5mg, 10 subjects (8 for TPN-672, 2 for placebo)
1mg single doseTPN-672single dose of 1mg, 10 subjects (8 for TPN-672, 2 for placebo)
2mg single doseTPN-672single dose of 2mg, 10 subjects (8 for TPN-672, 2 for placebo)
3mg single doseTPN-672single dose of 3mg, 10 subjects (8 for TPN-672, 2 for placebo)
4mg single doseTPN-672single dose of 4mg, 10 subjects (8 for TPN-672, 2 for placebo)
Primary Outcome Measures
NameTimeMethod
ACR48 hours

Apparent Clearance Rate

ADV48 hours

Apparent Distribution Volume

Cmax48 hours

Maximum Plasma Concentration

AUC48 hours

Area Under the Curve

Tmax48 hours

Time to Cmax

T1/248 hours

Time of half life

Adverse events48 hours

Number of Subjects with adverse events during clinical trial

Secondary Outcome Measures
NameTimeMethod
prolactin48 hours

serum prolactin test

temperature48 hours

ear temperature

pulse rate48 hours

pulse rate

IL-148 hours

Serum concentration of Interleukin-1

QTc48 hours

QTc interval

IL-248 hours

Serum concentration of Interleukin-2

INF-gamma48 hours

Serum concentration of Interferon-gamma

TNF-alpha48 hours

Serum concentration of Tumor necrosis factor-alpha

5-HT48 hours

Serum concentration of serotonin

DA48 hours

Serum concentration of Dopamine

NE48 hours

Serum concentration of Norepinephrine

BDNF48 hours

Serum concentration of Brain-derived neurotrophic factor

Glutamic acid48 hours

Serum concentration of Glutamic acid

GABA48 hours

Serum concentration of gamma-aminobutyric acid

respiratory48 hours

frequency of respiratory per minute

blood pressure48 hours

lying blood pressure, systolic and diastolic

electrocardiogram(ECG)48 hours

the number of subjects with abnormal ECG report by 12-lead electrocardiogram

IL-448 hours

Serum concentration of Interleukin-4

Extrapyramidal symptoms48 hours

Simpson Angus Rating Scale (SAS), total score ranges from 0 to 40, of which lower values represent a better outcome.

Involuntary Movement48 hours

Abnormal Involuntary Movement Scale (AIMS), total score ranges from 0 to 14, of which lower values represent a better outcome.

Akathisia48 hours

Barnes Akathisia Rating Scale (BARS), total score ranges from 0 to 40, of which lower values represent a better outcome.

IL-648 hours

Serum concentration of Interleukin-6

Trial Locations

Locations (1)

Shanghai Mental Health Center

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Shanghai, Shanghai, China

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