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

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.

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.

Study Overview

• Status: Unknown
• Conditions: PHA1A
• Intervention / Treatment: Drug: TPN-672

• Study Type: Interventional
• Enrollment (Anticipated): 62
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Mental Health Center
      • Contact: Huafang LI, MD PhD; Phone Number: 86-21-34773107; Email: lhlh_5@163.com
      • Principal Investigator: Huafang LI, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Jiangsu Kanion Pharmaceutical Co.
• Investigators: Study Director: Yifeng SHEN, MD PhD, Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2019
• Primary Completion (Anticipated): October 17, 2020
• Study Completion (Anticipated): December 17, 2020

Study Registration Dates

• First Submitted: April 13, 2019
• First Submitted That Met QC Criteria: April 26, 2019
• First Posted (Actual): April 30, 2019

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: pharmacokinetics; pharmacodynamics; tolerance; TPN-672
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Maleic acid
• Other Study ID Numbers: SMHC-180; TPN672-KYHY-201801 (Other Identifier: Kanion Pharmaceutical)

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