An Open Label Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BAY 1841788 in Japanese Subjects With Metastatic Castration-resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 9
- 主要终点
- Number of participants with Treatment Emergent Adverse Event as measure of safety and tolerability
研究概览
简要总结
The primary objectives of this study are to investigate the safety and tolerability of BAY 1841788 in Japanese subjects with metastatic castration-resistant prostate cancer (mCRPC) and the PK of BAY 1841788 and its major metabolite BAY 1896953.
详细描述
The drug product is licensed from Orion pharma, Finland which is also the manufacturer of the product.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Japanese males aged ≥ 20 years
- •Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features
- •Patients with metastatic castration-resistant prostate cancer (mCRPC). CRPC is defined as follows
- •Ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) analogue or antagonist, or bilateral orchiectomy, and castrate level of serum testosterone (< 1.7 nmol/l [50 ng/dL]) at screening AND
- •Progressive disease and/or prostate-specific antigen (PSA) increase of three consecutive rises, at least 1 week apart AND
- •PSA > 2ng/mL at screening
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1
- •Life expectancy of at least 3 months
- •Blood counts at screening: haemoglobin ≥ 9.0 g/dL, absolute neutrophil count ≥ 1,500/μL (1.5x109/l), platelet count ≥ 100,000/μL (100x109/l) (patient must not have received any growth factor or blood transfusion within 7 days of the hematology laboratory obtained at screening)
- •Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 x ULN, albumin > 3.0 g/dl
- •Prior treatment with antiandrogen. Discontinuation of bicalutamide or nilutamide (not approved in Japan) at least 6 weeks and other antiandrogens at least 4 weeks prior to the start of the study drug administration.
排除标准
- •Known metastases in the brain
- •Symptomatic local-regional disease that requires medical intervention including moderate/severe urinary obstruction or hydronephrosis due to prostate cancer
- •Acute toxicities (except for alopecia and CTCAE grade 2 neuropathy) of prior treatments and procedures not resolved to CTCAE ≤ grade 1 or baseline before the first drug administration
- •Febrile neutropenia of Common Terminology Criteria for Adverse Events (CTCAE) ≥ 3
- •History of other malignancy within the previous 5 years except a basal cell carcinoma of skin and any other cancer for which treatment has been completed ≥ 5 years ago and from which the patient has been disease-free5 years ago and from which the patient has been disease-free
- •Prior treatment within 4 weeks before the first drug administration with immunotherapy, antiandrogen, CYP17 inhibitor (CYP17i), oral ketoconazole, estrogens, 5-α reductase inhibitors or investigational treatment
- •Use of bicalutamide or nilutamide (not approved in Japan) within 6 weeks before the first drug administration
- •Radiation therapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) or chemotherapy (except for nitrosoureas and mitomycin C) within 4 weeks before the first drug administration. Use of nitrosoureas or mitomycin C within 6 weeks before the first drug administration.
- •Prior use of any herbal products known to decrease PSA levels (e.g. PC SPES or saw palmetto) within 4 weeks before the first drug administration
研究组 & 干预措施
BAY 1841788(ODM-201)
Cohort 1: Safety, tolerability and PK of 300 mg dose given twice daily. Escalation to cohort 2 in case no safety relevant adverse event has been observed within 28 days after start of multiple dose (MD) Cohort 2: Safety, tolerability and PK of 600 mg dose given twice daily
干预措施: BAY 1841788(ODM-201) (Drug)
结局指标
主要结局
Number of participants with Treatment Emergent Adverse Event as measure of safety and tolerability
时间窗: Up to 12 weeks
The intensity of an adverse event graded using the NCI CTCAE version 4.03
时间窗: Up to 12 weeks
National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE)
Plasma concentration of BAY 1841788 characterized by tmax
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
tmax: time to reach maximum drug concentration in plasma after single (first) dose
Plasma concentration of BAY 1841788 characterized by AUC(0-12)
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
AUC(0-12):AUC from time 0 to 12 hours after administration
Plasma concentration of diastereomers BAY 1896952 characterized by AUC(0-12)
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
AUC(0-12):AUC from time 0 to 12 hours after administration
Plasma concentration of BAY 1841788 characterized by Cmax
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
Cmax: maximum drug concentration in plasma after single dose administration
Plasma concentration of metabolite BAY 1896953 characterized by tmax
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
tmax: time to reach maximum drug concentration in plasma after single (first) dose
Plasma concentration of diastereomers BAY 1896951 characterized by Cmax
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
Cmax: maximum drug concentration in plasma after single dose administration
Plasma concentration of diastereomers BAY 1896951 characterized by AUC(0-12)
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
AUC(0-12):AUC from time 0 to 12 hours after administration
Plasma concentration of metabolite BAY 1896953 characterized by Cmax
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
Cmax: maximum drug concentration in plasma after single dose administration
Plasma concentration of diastereomers BAY 1896952 characterized by tmax
时间窗: tmax: time to reach maximum drug concentration in plasma after single (first) dose
Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
Plasma concentration of metabolite BAY 1896953 characterized by AUC(0-12)
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
AUC(0-12):AUC from time 0 to 12 hours after administration
Plasma concentration of diastereomers BAY 1896951 characterized by tmax
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
tmax: time to reach maximum drug concentration in plasma after single (first) dose
Plasma concentration of diastereomers BAY 1896952 characterized by Cmax
时间窗: Day -5 {pre dose, 0.5,1,1.5,3,5 ,8,12,24,36,48},Day -2 {before morning dose, 0.5,1,1.5,3,5,8, 12, 24, 36 and 48 h} ,Day 7 {before morning dose, 0.5, 1, 1.5,3,5,8,12 h (before evening dose)}
Cmax: maximum drug concentration in plasma after single dose administration
次要结局
未报告次要终点