Primary objectives of this study are to assess the safety and tolerability of BAY 1163877 in Japanese subjects with refractory, locally advanced or metastatic solid tumors and to characterize the PK of BAY 1163877
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Cohort 1: Single dose 600 mg on day 1, no drug on day 2 and then twice daily administration of the same dose for the remaining 19 days of cycle 1. From cycle 2 onwards all subjects are continuously treated for 21 days per cycle with twice daily administration of the same dose. Cohort 2: Single dose 800 mg on day 1, no drug on day 2 and then twice daily administration of the same dose for the remaining 19 days of cycle 1. From cycle 2 onwards all subjects are continuously treated for 21 days per cycle with twice daily administration of the same dose.
Unnamed facility
Kashiwa, Chiba, Japan
Unnamed facility
Koto-ku, Tokyo, Japan
Number of an Treatment Emergent Adverse Event
Time frame: Up to 35 days after the last study drug administration
Intensity of an Treatment Emergent Adverse Event graded using the NCI-CTCAE version 4.03
Time frame: Up tp 35 days after the last study drug administration
Maximum observed plasma concentration after single dose administration (Cmax) of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
Cmax divided by dose (mg) per kg body weight (Cmax,norm) of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
Cmax divided by dose (mg) (Cmax/D) of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
Area under the plasma concentration vs time curve from zero to 12 hours p.a. after first-dose administration (AUC(0-12)) of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
AUC(0-12) divided by dose (mg) per kg body weight (AUC(0-12) norm) of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
AUC(0-12) divided by dose (mg) (AUC(0-12)/D) of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
AUC from time zero to the last data point > LLOQ (lower limit of quantification) of BAY1163877 (AUC(0-tlast))
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Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUC(0-tlast) divided by dose (mg) per kg body weight (AUC(0-tlast) norm) of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUC(0-tlast) divided by dose (mg) (AUC(0-tlast)/D) of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUC of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUCnorm of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
AUC/D of BAY1163877
Time frame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
Maximum Observed Drug Concentration in Plasma after multiple administrations (Cmax, md) of BAY1163877
Time frame: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Cmax after multiple administrations divided by dose (mg) per kg body weight (Cmax,norm, md) of BAY1163877
Time frame: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Cmax after multiple administrations divided by dose (mg) (Cmax/Dmd) of BAY1163877
Time frame: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12) after multiple administrations (AUC(0-12)md) of BAY1163877
Time frame: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-12)norm,md) of BAY1163877
Time frame: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12) divided by dose (mg) after multiple administrations (AUC(0-12)/Dmd) of BAY1163877
Time frame: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast)after multiple administrations (AUC(0-tlast)md) of BAY1163877
Time frame: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-tlast) norm,md) of BAY1163877
Time frame: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast) after multiple administrations divided by dose (mg) (AUC(0-tlast)/Dmd) of BAY1163877
Time frame: On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Tumor response evaluation based on RECIST 1.1
Time frame: Screening, end of every second cycle (i.e., Cycle 2, 4, 6, 8,…)
FGF23 levels
FGF 23: fibroblast growth factor 23
Time frame: Cycle 1 (Days 1 and 15)
Phosphate levels
Time frame: Cycle 1 (Days 1, 8, 15), Cycle 2 to 12 (Days 1, 8, 15), Cycle ≥13 (Days 1, 11), end of treatment
FGFR1/2/3 mRNA expression in tumor tissue to evaluate of biomarker status
Time frame: At Screening visit