Japanese BAY1000394 Monotherapy Phase I Study

An Open-label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics of BAY1000394 Given in a 3 Days on / 4 Days Off Schedule in Japanese Subjects With Advanced Malignancies

This is an open-label, non-randomized, dose-escalating Phase I study to evaluate the safety, tolerability, pharmacokinetics of BAY1000394 given in a 3 days on / 4 days off schedule in Japanese subjects with advanced malignancies.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BAY1000394 (2.5mg); Drug: BAY1000394 (5mg)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 811-1395
  • 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: All

Description

Inclusion Criteria:

• Japanese male or female subjects aged ≥20 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• Life expectancy of at least 12 weeks
• Subjects with advanced, histologically or cytologically confirmed solid tumors, not amenable to any standard therapy, have no standard therapy available, or subjects must have actively refused any treatment which would be regarded standard, and if in the judgment of the investigator, experimental treatment is clinically and ethically acceptable
• At least 1 tumor lesion evaluable by computer tomography (CT) or scan or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Adequate bone marrow, liver, and renal functions

Exclusion Criteria:

• Anticancer chemotherapy or immunotherapy within 4 weeks of study entry. Mitomycin C or nitrosoureas should not be given within 6 weeks of study entry.
• Radiotherapy to target lesions within 3 weeks prior to the first dose of study drug.
• Use of biological response modifiers, such as granulocyte colony-stimulating factor (G-CSF), within 3 weeks prior to the first dose of study drug.
• Symptomatic metastatic brain or meningeal tumors.
• Investigational drug treatment outside of this study during or within 4 weeks prior to study entry.
• Blood pressure <100/60 mmHg or pulse >100 BPM

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: BAY1000394; Approximately 12 subjects will be included: 3 to 6 evaluable subjects for each cohort. The cycle length will be 3 weeks (21 days).	Drug: BAY1000394 (2.5mg); BAY1000934 2.5mg twice a day (bid) in a 3 days on and 4 days off schedule. (Cohort 1); Drug: BAY1000394 (5mg); BAY1000934 5mg twice a day (bid) in a 3 days on and 4 days off schedule. (Cohort 2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events as a measure of safety and tolerability	6 months
Number of participants with abnormal lab parameters based on descriptive statistics	6 months
Maximum observed drug concentration (Cmax) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
Cmax divided by dose per body weight (Cmax,norm) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
Cmax divided by dose (Cmax/D) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
Area under the concentration versus time curve from zero to infinity after single dose (AUC) for BAY1000394 and its metabolite M-1	= Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose)
AUC from time 0 to 12 hours after single dose (AUC(0-12) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8 and 12 hours
AUC divided by dose per body weight (AUCnorm) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose)
AUCnorm from time 0 to 12 hours after single dose (AUC(0-12),norm) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8 and 12 hours
AUC divided by dose (AUC/D) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose)
Time to reach Cmax (tmax) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
Terminal half-life (t½) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 1: 0 (pre dose), 0.5, 1, 2, 4, 6, 8, 12 and 24 hours (Day 2, before morning dose). Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
Maximum observed drug concentration after multiple dosing (Cmax,md) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
Cmax divided by dose per body weight after multiple dosing (Cmax,norm,md) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
Cmax divided by dose (Cmax,md/D) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
AUC from time 0 to 12 hours after multiple dosing (AUC(0-12),md) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
AUCnorm from time 0 to 12 hours after multiple dosing (AUC(0-12),norm,md) for BAY1000394 and its metabolite M-1	Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)
AUC from time 0 to 12 hours divided by dose after multiple dosing for BAY1000394 and its metabolite M-1	Cycle 1 / Day 10 : 0 (before morning dose), 0.5, 1, 2, 4, 6, 8 and 12 hours (before evening dose)

Secondary Outcome Measures

Outcome Measure	Time Frame
Tumor response	Screening and on Day 21 of even numbered cycle

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer products.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2014
• Primary Completion (Actual): January 6, 2015
• Study Completion (Actual): July 19, 2018

Study Registration Dates

• First Submitted: January 27, 2014
• First Submitted That Met QC Criteria: January 27, 2014
• First Posted (Estimate): January 28, 2014

Study Record Updates

• Last Update Posted (Actual): June 24, 2019
• Last Update Submitted That Met QC Criteria: June 20, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Japanese; Advanced malignancies; CDK inhibitor; BAY1000394
• Other Study ID Numbers: 15200

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No