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

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

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.

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: BAY 1841788(ODM-201)

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: BAY 1841788(ODM-201); 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.

What is the study measuring?

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)}

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2015
• Primary Completion (Actual): November 19, 2015
• Study Completion (Actual): January 18, 2018

Study Registration Dates

• First Submitted: February 10, 2015
• First Submitted That Met QC Criteria: February 13, 2015
• First Posted (Estimate): February 16, 2015

Study Record Updates

• Last Update Posted (Actual): January 25, 2018
• Last Update Submitted That Met QC Criteria: January 24, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Castration-resistant prostate cancer (CRPC); Metastatic castration-resistant prostate cancer; Neoplasm Metastasis
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 17719