Chronic graft-versus-host disease after at least 1 line of systemic therapy
Conditions
Interventions
placebo 200mg single oral administration group:placebo 200mg administered orally as a single dose
BN101 200mg group:BN101 tablets, 200mg
placebo 400mg single oral administration group:placebo 400mg administered orally as a single dose
BN101 400mg group:BN101 tablets, 400mg
Sponsors
Xuzhou Medical University Affiliated Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years and < 46 years, male or female. 2. Body mass index (BMI) ranging from 19 to 24 kg/m^2. 3. Normal and healthy as assessed by the following procedures: Comprehensive clinical assessment (detailed medical history and complete physical examination); Normal subjects with clinical laboratory tests (hematology, chemistry, urinalysis) within normal ranges or clinically acceptable. 4. Absence of 12-lead ECG abnormalities that, the investigator assessed, were clinically significant or would potentially affect the safety of the subject at screening. 5. Before enrollment, subjects should test negative for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, and human immunodeficiency virus (HIV). For subjects who were HBsAg negative but hepatitis B core antibody (HBcAb) positive, HBV-DNA testing should be negative. 6. During the screening period, serum pregnancy tests for women of childbearing potential should be negative. Women of childbearing potential were defined as sexually mature women who had not undergone hysterectomy or who had menstruated in the previous 12 months. However, if amenorrhea could have resulted from prior chemotherapy, anti-estrogen therapy, or ovarian suppression, women with amenorrhea of 12 months or more were still considered women of childbearing potential. 7. Sexually active women of childbearing potential enrolled in this study must agree to use 2 approved methods of contraception throughout the trial and within 3 months following the last dose. Effective contraceptions included: Intrauterine device plus one barrier contraception; 2 barrier contraceptions. Effective barrier methods were male or female condoms, diaphragms, and spermicides (creams or gels containing spermicidal chemicals); or Vasectomy. 8. Sexually active male subjects with partners of childbearing potential must agree to use 2 accepted methods of contraception (as defined in Criterion 7 above) during the trial and within 3 months following the last dose. 9. Subjects must be fully informed of the study and able to give written informed consent prior to any trial-specific procedures and be willing to complete all study tests and assessments in accordance with the protocol and visit schedule. 10. Smokers smoking less than 10 cigarettes per day could be enrolled, but subjects were required to refrain from smoking while receiving the investigational drug and during follow-up assessments until completion of the last PK sample collection.
Exclusion criteria
Exclusion criteria: 1. In the judgment of the investigator, the subject's past or present illness could potentially interfere with the investigational drug or study procedures, could have a potential impact on the subject's safety, and could affect the PK assessments. 2. Subjects had used prescription drugs within 14 days or over-the-counter drugs (including traditional Chinese medicine, vitamins, Chinese herbal medicine, dietary supplements, etc.) within 48 hours or grapefruit or grapefruit juice within 7 days prior to investigational drug administration. 3. Excessive drinkers (defined as consuming more than 14 alcohol units per week within 4 weeks prior to screening): 1 unit = 285 mL of beer containing about 3.5% alcohol, or 25 mL of spirits containing about 40% alcohol, or 100 mL of wine containing about 10% alcohol). 4. Drug or psychotropic dependence within 2 years prior to enrollment. 5. Positive breath alcohol test or positive urine drug screen at screening or admission. 6. Subjects complicated with active gastrointestinal diseases requiring drug therapy. 7. Subjects complicated with liver disease, and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) > 1.5 × ULN, and total bilirubin (TBIL) > ULN at screening. 8. Subjects complicated with renal diseases, and/or serum creatinine > ULN at screening. 9. Taking proton pump inhibitors (e.g., rabeprazole, omeprazole) or CYP3A4 inducers (e.g., rifampin, phenobarbital). 10. Subjects who were participating in a clinical trial with another investigational drug at the time of enrollment or had used any investigational drug within 28 days (or 5 half-lives, whichever was longer) prior to enrollment or had received or been exposed to 4 or more new investigational drugs within 12 months prior to enrollment. 11. Subjects who had donated more than 500 mL of blood within 3 months prior to enrollment. 12. Pregnant or lactating women. 13. Known hypersensitivity to the active ingredients or excipients of the investigational drug, or to other selective Rho-associated protein kinase 2 (ROCK2) inhibitors. 14. Corrected QT interval by Fridericia's formula (QTcF) > 450 ms at screening or prior to investigational drug administration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events;Serious adverse events;Adverse events related to the investigational drug;Vital signs;Physical examination;Laboratory tests;12-lead ECG; | — |
Secondary
| Measure | Time frame |
|---|---|
| Concentrations of BN101 in plasma;Concentrations of Metabolite m1 in plasma;Concentrations of Metabolite m2 in plasma; | — |
Countries
China
Contacts
Public ContactZhenyu Li
Xuzhou Medical University Affiliated Hospital
Outcome results
None listed