Evaluate the Safety, Tolerability and Pharmacokinetic Profile of TPN672 Tablets Maleate in Patients With Schizophrenia

NCT05192304 | Unknown Phase 1 DMC

• 1 other identifier: BR-2020-1491-TPN672
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ib clinical study of TPN672 maleate in patients with schizophrenia

Conditions

Schizophrenia

Keywords

Phase Ib; CHINA

Outcome Measures

Primary Outcomes (5)

• Adverse events

  Incidence of Adverse Events

  follow-up visit from the beginning of the dose to the day 14 after the last dose

• Blood pressure

  Safety indicator,Blood pressure is recorded in millimeters of mercury

  Day 14

• Respiration

  Safety indicator，the unit of recording is the number of breaths per minute.

  Day 14

• Heart rate

  Safety indicator，the unit of heart rate is the number of heartbeats per minute.

  Day 14

• Temperature

  Safety indicator,Body temperature is recorded in degrees Celsius

  Day 14

Secondary Outcomes (11)

• Maximum plasma concentration (Cmax)

  240 hours

• Time to maximum plasma concentration (Tmax)

  240 hours

• Area under the curve (AUC)

  240 hours

• steady state minimal concentration（Css_min）

  240hours

• Elimination half-life (t1/2)

  30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours ,days 8-14 after the last dose.

Study Arms (6)

0.2mg single dose

EXPERIMENTAL

single dose of TPN-672 0.2mg, 2 subjects

Drug: TPN-672

0.3mg single dose

EXPERIMENTAL

single dose of TPN-672 0.3mg, 12 subjects（9 for TPN-672, 3 for placebo）

Drug: TPN-672

0.4mg single dose

EXPERIMENTAL

single dose of TPN-672 0.4mg, 12 subjects（9 for TPN-672, 3 for placebo）

Drug: TPN-672

0.5mg single dose

EXPERIMENTAL

single dose of TPN-672 0.5mg, 12 subjects（9 for TPN-672, 3 for placebo）

Drug: TPN-672

0.6mg single dose

EXPERIMENTAL

single dose of TPN-672 0.6mg, 12 subjects（9 for TPN-672, 3 for placebo）

Drug: TPN-672

0.7mg single dose

EXPERIMENTAL

single dose of TPN-672 0.7mg, 12 subjects（9 for TPN-672, 3 for placebo）

Drug: TPN-672

Interventions

TPN-672 DRUG

single dose of TPN-672 maleate tablet

Also known as: single dose of TPN-672 maleate tablet

0.2mg single dose; 0.3mg single dose; 0.4mg single dose; 0.5mg single dose; 0.6mg single dose; 0.7mg single dose

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old ≤ age ≤ 65 years old at the time of signing the informed consent form, male or female.
• kg/m2 ≤ body mass index (BMI) ≤ 30kg/m2, and weight ≥ 50kg for men and ≥ 45kg for women.
• Subjects met DSM-5 diagnostic criteria for a confirmed diagnosis of schizophrenia and were stable within the past 6 months as assessed by the investigator.
• Subjects are currently taking aripiprazole, olanzapine or risperidone monotherapy for schizophrenia at a dose not exceeding the maximum dose specified in the instructions and the dose and frequency of administration have not changed in the last 1 month.
• Screening period PANSS scale total score \<70, PANSS scale individual score of positive symptom items ≤3, CGI-S score ≤4.
• Individual scores were ≤1 on the SAS scale, ≤2 on the AIMS scale, and ≤2 on item 4 of the BARS scale, "Overall clinical assessment of sedentary inability" during the screening period.
• Female and male subjects of childbearing potential and their spouses must be able to secure effective contraception (medically approved contraception such as IUDs, the pill or condoms) during the study and for 6 months after the end of the drug administration.
• Subjects and their guardians fully understand the purpose and requirements of the trial, voluntarily participate in the clinical trial and sign a written informed consent form, and are willing to complete the entire trial process according to the trial requirements.

You may not qualify if:

• Subjects met DSM-5 criteria for other psychiatric disorders.
• Subjects were administered strong inducers/strong inhibitors of CYP2D6, CYP3A4, CYP3A5, CYP2C9 for 5 half-lives prior to the first dose.
• Subjects were on long-acting antipsychotics for 6 months prior to their first dose.
• Received electroconvulsive therapy, transcranial magnetic stimulation (rTMS) within 1 month prior to screening
• Those who answered "yes" to questions 4 or 5 of the suicidal ideation entry on the Columbia Suicide Scale (C-SSRS) during the screening period, or who were currently or within the past 12 months significantly suicidal, or who were considered to be at risk for suicidal and violent behavior based on the investigator's clinical assessment.
• Those with abnormal physical examination or vital signs during the screening period that are clinically significant.
• Abnormal laboratory tests during the screening period that the investigator determines to be clinically significant, e.g., liver: ALT or AST≥ 1.2 times the upper limit of normal; kidney: Cr\> the upper limit of normal value.
• Prolactin ≥ 5 times the upper limit of normal during the screening period.
• Screening subjects with systolic blood pressure \<90 mmHg or \>140 mmHg and diastolic blood pressure \< 60mmHg or \>90mmHg.
• Patients with poorly controlled diabetes (fasting glucose ≥ 10 mmol/L), or are On insulin for diabetes, or at screening with a primary diagnosis of type 2 diabetes.
• Screening QTc interval \>450ms (men) or 470ms (women), or family history of long QT interval syndrome, or combined cardiac insufficiency, severe arrhythmia or ischemic heart disease requiring medication, congenital heart disease, severe organic heart disease or history of such disease.
• Combined with convulsive disorders such as epilepsy (except febrile convulsions)
• Current or previous hyper- or hypothyroidism, Parkinson's disease, malignancy.
• Tobacco addiction within 1 year prior to screening, with an average of \>10 cigarettes or equivalent per day.
• Alcohol consumption within 1 year prior to screening, with an average weekly intake of more than 14 units of alcohol (1 unit = 285 ml of beer or 25 ml of spirits or 150 ml of wine) or a positive breath test for alcohol.

Sponsors & Collaborators

• Jiangsu Kanion Pharmaceutical Co., Ltd: lead
• Shanghai Mental Health Center: collaborator

Study Sites (1)

Shanghai Mental Health Center

Shanghai, Shanghai Municipality, 200030, China

Location

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Li Huafang, MD PhD

  Shanghai Mental Health Center

  PRINCIPAL INVESTIGATOR

• Li Guanjun

  Shanghai Mental Health Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhao Binjiang

CONTACT

86-518-85521987; 13466570402@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2021
• First Posted: January 14, 2022
• Study Start: February 1, 2022
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2024
• Last Updated: January 14, 2022

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)