Phase 1 Dose Escalation Study of BAY 1841788 in Japanese Metastatic Castration-resistant Prostate Cancer (mCRPC) Subjects

Study Overview
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Brief Summary
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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.

Detailed Description
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The drug product is licensed from Orion pharma, Finland which is also the manufacturer of the product.

Official Title
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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

Conditions
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Prostatic Neoplasms

Intervention / Treatment
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* Drug: BAY 1841788(ODM-201)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY 1841788(ODM-201)<br>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 | Drug: BAY 1841788(ODM-201)<br>* Cohort 1: Single dose 300 mg BAY 1841788, followed by twice daily administration of the same dose for 12 weeks Cohort 2: Single dose 2x300 mg BAY 1841788, followed by twice daily administration of the same dose for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Treatment Emergent Adverse Event as measure of safety and tolerability |  | Up to 12 weeks | 
| The intensity of an adverse event graded using the NCI CTCAE version 4.03 | National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE) | Up to 12 weeks | 
| Plasma concentration of BAY 1841788 characterized by Cmax | Cmax: maximum drug concentration in plasma after single dose administration | 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 BAY 1841788 characterized by tmax | 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 BAY 1841788 characterized by AUC(0-12) | AUC(0-12):AUC from time 0 to 12 hours after administration | 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 Cmax | Cmax: maximum drug concentration in plasma after single dose administration | 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 tmax | 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) | AUC(0-12):AUC from time 0 to 12 hours after administration | 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 diastereomers BAY 1896951 characterized by Cmax | Cmax: maximum drug concentration in plasma after single dose administration | 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 diastereomers BAY 1896951 characterized by tmax | 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 diastereomers BAY 1896951 characterized by AUC(0-12) | AUC(0-12):AUC from time 0 to 12 hours after administration | 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 diastereomers BAY 1896952 characterized by Cmax | Cmax: maximum drug concentration in plasma after single dose administration | 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 diastereomers BAY 1896952 characterized by tmax | 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 AUC(0-12) | AUC(0-12):AUC from time 0 to 12 hours after administration | 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)} | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasm Metastasis, Metastatic castration-resistant prostate cancer, Castration-resistant prostate cancer (CRPC)