Clinical trial NCT05192304: Evaluate the Safety, Tolerability and Pharmacokinetic Profile of TPN672 Tablets Maleate in Patients With Schizophrenia
Official title: A Randomized, Double-blind, Placebo-controlled, Dose-escalation Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetic Profile of Multiple Doses of TPN672 Tablets Maleate in Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Schizophrenia
Keywords: Phase Ib
CHINA
Lead sponsor: Jiangsu Kanion Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Mental Health Center
First posted: 2022-01-14
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: This is a single-center, randomized, double-blind, placebo-controlled, dosion-increasing, Phase Ib clinical study evaluating the safety, tolerability, and pharmacokinetic characteristics of multiple doses of TPN672 maleate in patients with schizophrenia

Eligibility criteria: Inclusion Criteria:

1. 18 years old ≤ age ≤ 65 years old at the time of signing the informed consent form, male or female.
2. 18.5kg/m2 ≤ body mass index (BMI) ≤ 30kg/m2, and weight ≥ 50kg for men and ≥ 45kg for women.
3. 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.
4. 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.
5. Screening period PANSS scale total score \<70, PANSS scale individual score of positive symptom items ≤3, CGI-S score ≤4.
6. 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.
7. 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.
8. 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.

Exclusion Criteria:

1. Subjects met DSM-5 criteria for other psychiatric disorders.
2. Subjects were administered strong inducers/strong inhibitors of CYP2D6, CYP3A4, CYP3A5, CYP2C9 for 5 half-lives prior to the first dose.
3. Subjects were on long-acting antipsychotics for 6 months prior to their first dose.
4. Received electroconvulsive therapy, transcranial magnetic stimulation (rTMS) within 1 month prior to screening
5. 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.
6. Those with abnormal physical examination or vital signs during the screening period that are clinically significant.
7. 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.
8. Prolactin ≥ 5 times the upper limit of normal during the screening period.
9. Screening subjects with systolic blood pressure \<90 mmHg or \>140 mmHg and diastolic blood pressure \< 60mmHg or \>90mmHg.
10. 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.
11. 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.
12. Combined with convulsive disorders such as epilepsy (except febrile convulsions)
13. Current or previous hyper- or hypothyroidism, Parkinson's disease, malignancy.
14. Tobacco addiction within 1 year prior to screening, with an average of \>10 cigarettes or equivalent per day.
15. 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.
16. Persons with a history of drug or substance abuse within 1 year prior to screening or a positive urine drug screen.
17. Subjects who may be hypersensitive to any of the components of this drug.
18. HIV antibody, HBsAg, HCV antibody or positive syphilis serology results.
19. History of significant blood loss or blood loss ≥ 200 ml in the 3 months prior to screening
20. Enrolled in another clinical trial within 3 months prior to screening, or currently participating in a clinical trial.
21. Women who are expecting or breastfeeding.
22. The investigator did not consider it appropriate to participate in this trial.

Primary outcomes:
measure: Adverse events
timeFrame: follow-up visit from the beginning of the dose to the day 14 after the last dose
measure: Blood pressure
timeFrame: Day 14
measure: Respiration
timeFrame: Day 14
measure: Heart rate
timeFrame: Day 14
measure: Temperature
timeFrame: Day 14
Secondary outcomes:
measure: Maximum plasma concentration (Cmax)
timeFrame: 240 hours
measure: Time to maximum plasma concentration (Tmax)
timeFrame: 240 hours
measure: Area under the curve (AUC)
timeFrame: 240 hours
measure: steady state minimal concentration（Css_min）
timeFrame: 240hours
measure: Elimination half-life (t1/2)
timeFrame: 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours, 12 hours ,days 8-14 after the last dose.
measure: Positive and Negative Syndrome Scale
timeFrame: Follow-up visit on the day 14 after the last dose
measure: Clinical Global Impression sions scale
timeFrame: Follow-up visit on the day 14 after the last dose
measure: Calgary Depression Scale for Schizophrenia
timeFrame: Follow-up visit on the day 14 after the last dose
measure: Blood coagulation function
timeFrame: Day 14
measure: 12-lead ECG
timeFrame: Day 14
measure: Serum prolactin ( PRL)
timeFrame: Day 14
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
Study officials:
affiliation: Shanghai Mental Health Center
name: Li Huafang, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Mental Health Center
name: Li Guanjun
role: PRINCIPAL_INVESTIGATOR
References: