Clinical trial NCT03931668: Tolerance, PK and PD Effects Study of TPN-672 in Chinese Healthy Volunteers
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: PHA1A
Keywords: tolerance
pharmacokinetics
pharmacodynamics
TPN-672
Lead sponsor: Shanghai Mental Health Center
Sponsor class: OTHER
Collaborators: name: Jiangsu Kanion Pharmaceutical Co.
First posted: 2019-04-30
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: 48 hours
measure: Cmax
timeFrame: 48 hours
measure: AUC
timeFrame: 48 hours
measure: Tmax
timeFrame: 48 hours
measure: T1/2
timeFrame: 48 hours
measure: ACR
timeFrame: 48 hours
measure: ADV
timeFrame: 48 hours
Secondary outcomes:
measure: prolactin
timeFrame: 48 hours
measure: temperature
timeFrame: 48 hours
measure: pulse rate
timeFrame: 48 hours
measure: respiratory
timeFrame: 48 hours
measure: blood pressure
timeFrame: 48 hours
measure: electrocardiogram(ECG)
timeFrame: 48 hours
measure: QTc
timeFrame: 48 hours
measure: Extrapyramidal symptoms
timeFrame: 48 hours
measure: Involuntary Movement
timeFrame: 48 hours
measure: Akathisia
timeFrame: 48 hours
measure: IL-6
timeFrame: 48 hours
measure: IL-4
timeFrame: 48 hours
measure: IL-1
timeFrame: 48 hours
measure: IL-2
timeFrame: 48 hours
measure: INF-gamma
timeFrame: 48 hours
measure: TNF-alpha
timeFrame: 48 hours
measure: 5-HT
timeFrame: 48 hours
measure: DA
timeFrame: 48 hours
measure: NE
timeFrame: 48 hours
measure: BDNF
timeFrame: 48 hours
measure: Glutamic acid
timeFrame: 48 hours
measure: GABA
timeFrame: 48 hours
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
Study officials:
affiliation: Shanghai Mental Health Center
name: Yifeng SHEN, MD PhD
role: STUDY_DIRECTOR
References: