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Pharmacokinetics and Safety of Regorafenib (BAY73-4506) in Cancer Subjects With Severe Renal Impairment

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ClinicalTrials.gov Identifier: NCT01853046
Recruitment Status : Completed
First Posted : May 14, 2013
Results First Posted : February 20, 2017
Last Update Posted : February 20, 2017
Sponsor:
Information provided by (Responsible Party):
Bayer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms
Intervention Drug: Regorafenib (Stivarga, BAY73-4506)
Enrollment 24
Recruitment Details Overall, 39 adult male or female participants with locally advanced and / or metastatic solid tumors were screened at 4 study centers in Canada and 4 study centers in the USA.
Pre-assignment Details 15 participants (38.5% of 39) were screening failures and 24 participants received treatment with regorafenib. All 15 participants who failed to meet the inclusion and / or exclusion criteria were not assigned to study
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Period Title: Overall Study
Started 18 6
Received Treatment 18 6
Completed 0 0
Not Completed 18 6
Reason Not Completed
Withdrawal by Subject             1             1
Adverse Event             4             2
Disease progression             13             3
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment Total
Hide Arm/Group Description Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. Total of all reporting groups
Overall Number of Baseline Participants 18 6 24
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 6 participants 24 participants
62.0  (9.6) 64.2  (6.9) 62.5  (8.9)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 6 participants 24 participants
Female
9
  50.0%
4
  66.7%
13
  54.2%
Male
9
  50.0%
2
  33.3%
11
  45.8%
1.Primary Outcome
Title AUC(0-tlast) [Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point >LLOQ (Lower Limit of Quantification)] for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation. The AUC(0-tlast) [Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point >LLOQ (Lower Limit of Quantification)] is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Time Frame Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg*h/L
Regorafenib
67.2
(45.5%)
76.6
(50.3%)
Regorafenib metabolites M-2
27.8
(80.4%)
19.0
(58.7%)
Regorafenib metabolites M-5
5.25
(145%)
2.34
(79.8%)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment, Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Comments Point estimates (LS-means) and 2-sided exploratory 90% confidence intervals for AUC(0-tlast) of regorafenib calculated by re-transformation of the logarithmic data from ANOVAs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1.14
Confidence Interval (2-Sided) 90%
0.796 to 1.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment, Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Comments Point estimates (LS-means) and 2-sided exploratory 90% confidence intervals for AUC(0-tlast) of metabolites M-2 calculated by re-transformation of the logarithmic data from ANOVAs.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-means
Estimated Value 0.684
Confidence Interval (2-Sided) 90%
0.397 to 1.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment, Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Comments Point estimates (LS-means) and 2-sided exploratory 90% confidence intervals for AUC(0-tlast) of metabolites M-5 calculated by re-transformation of the logarithmic data from ANOVAs
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS-means
Estimated Value 0.446
Confidence Interval (2-Sided) 90%
0.200 to 0.996
Estimation Comments [Not Specified]
2.Primary Outcome
Title AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0-24 Hours Post Administration) for Metabolites M-7 and M-8
Hide Description Amount of drug excreted into urine during the collection interval 0-24 hours post dose was expressed as percentage of administered dose.
Time Frame Days 1-2: 0-24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 14 5
Mean (Standard Deviation)
Unit of Measure: percentage of dose
Regorafenib metabolites M-7 3.607  (1.124) 1.309  (0.649)
Regorafenib metabolites M-8 1.120  (0.737) 0.184  (0.229)
3.Secondary Outcome
Title AUC (Area Under the Plasma Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation. AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time Frame Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg*h/L
Regorafenib (n=6, 3)
59.5
(26.1%)
98.7
(71.0%)
Regorafenib metabolites M-2 (n=13, 4)
32.6
(89.0%)
20.8
(65.4%)
Regorafenib metabolites M-5 (n=0, 0)
NA [1] 
(NA%)
NA [1] 
(NA%)
[1]
Number of analyzed subjects is zero.
4.Secondary Outcome
Title AUC(0-24) (AUC From Time Zero to 24 Hours p.a. After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation. The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; AUC(0-24) is defined as AUC divided from zero to 24 hours after single (first) dose.
Time Frame Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
In Normal/mild renal impairment group, participants analyzed for regorafenib, M-2 and M-5 are n=18, 18, and 17 respectively. In Severe renal impairment group, participants analyzed for regorafenib, M-2 and M-5 are n=6, 6, and 5 respectively. Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg*h/L
Regorafenib
30.0
(39.8%)
28.4
(62.0%)
Regorafenib metabolites M-2
13.5
(70.0%)
7.93
(72.7%)
Regorafenib metabolites M-5
1.17
(116%)
0.474
(101%)
5.Secondary Outcome
Title Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation.Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Time Frame Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg/L
Regorafenib
2.45
(47%)
2.00
(69.7%)
Regorafenib metabolites M-2
1.01
(66.7%)
0.525
(69.6%)
Regorafenib metabolites M-5
0.0877
(125%)
0.0341
(67.0%)
6.Secondary Outcome
Title Tmax (Time to Reach Maximum Drug Concentration in Plasma After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation.Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Time Frame Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Median (Full Range)
Unit of Measure: h
Regorafenib
4.03
(1.00 to 24.0)
3.04
(1.00 to 23.75)
Regorafenib metabolites M-2
4.03
(1.00 to 24.0)
6.04
(1.98 to 23.8)
Regorafenib metabolites M-5
47.8
(6.00 to 96.1)
48.9
(24.1 to 95.8)
7.Secondary Outcome
Title Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description based on non-compartmental PK evaluation.
Time Frame Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Median (Full Range)
Unit of Measure: h
Regorafenib
95.7
(46.4 to 96.3)
95.8
(95.6 to 96.0)
Regorafenib metabolites M-2
95.7
(46.4 to 96.3)
95.8
(95.6 to 96.0)
Regorafenib metabolites M-5
95.7
(46.4 to 96.3)
95.8
(95.6 to 96.0)
8.Secondary Outcome
Title t1/2 (Half-life Associated With the Terminal Slope) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation. t1/2 refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in hours (h) and derived from the terminal slope of the concentration versus time curve.
Time Frame Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h
Regorafenib (n=6, 3)
28.7
(23.0%)
27.9
(32.0%)
Regorafenib metabolites M-2 (n=13, 4)
26.2
(25.7%)
25.5
(24.0%)
Regorafenib metabolites M-5 (n=0, 0)
NA [1] 
(NA%)
NA [1] 
(NA%)
[1]
Number of analyzed subjects is zero.
9.Secondary Outcome
Title CL/F (Total Body Clearance of Drug After Extravascular Administration) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation.Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/H
Regorafenib (n=6, 3)
2.69
(26.1%)
1.62
(71.0%)
Regorafenib metabolites M-2 (n=13, 4)
5.08
(89.0%)
7.95
(65.4%)
Regorafenib metabolites M-5 (n=0, 0)
NA [1] 
(NA%)
NA [1] 
(NA%)
[1]
Number of analyzed subjects is zero.
10.Secondary Outcome
Title Vz/F (Apparent Volume of Distribution During Terminal Phase After Single (First) Oral Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation.Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time Frame Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
Regorafenib (n=6, 3)
111
(31.9%)
65.2
(81.0%)
Regorafenib metabolites M-2 (n=13, 4)
192
(83.8%)
292
(71.1%)
Regorafenib metabolites M-5 (n=0, 0)
NA [1] 
(NA%)
NA [1] 
(NA%)
[1]
Number of analyzed subjects is zero.
11.Secondary Outcome
Title AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation.
Time Frame Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
In Normal/mild renal impairment group, number of participants analyzed is 13. In Severe renal impairment group, number of participants analyzed is 4. Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg*h/L
Regorafenib
56.0
(56.4%)
45.2
(45.8%)
Regorafenib metabolites M-2
53.9
(63.1%)
35.0
(207%)
Regorafenib metabolites M-5
49.7
(130%)
34.2
(438%)
12.Secondary Outcome
Title Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation.Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Time Frame Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 13 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg/L
Regorafenib
3.52
(54.9%)
2.87
(62.2%)
Regorafenib metabolites M-2
3.52
(58.8%)
2.29
(257%)
Regorafenib metabolites M-5
3.25
(133%)
2.23
(659%)
13.Secondary Outcome
Title AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description based on non-compartmental PK evaluation.
Time Frame Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 13 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mg*h/L
Regorafenib
133
(55.1%)
111
(54.8%)
Regorafenib metabolites M-2
136
(64.9%)
92.3
(280%)
Regorafenib metabolites M-5
183
(128%)
134
(459%)
14.Secondary Outcome
Title Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description based on non-compartmental PK evaluation
Time Frame Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 13 4
Median (Full Range)
Unit of Measure: h
Regorafenib
3.97
(0.000 to 23.8)
4.25
(0.000 to 10.0)
Regorafenib metabolites M-2
4.12
(0.000 to 23.9)
4.00
(0.000 to 10.0)
Regorafenib metabolites M-5
0.000
(0.000 to 24.0)
0.000
(0.000 to 8.00)
15.Secondary Outcome
Title Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description based on non-compartmental PK evaluation
Time Frame Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 13 4
Median (Full Range)
Unit of Measure: h
Regorafenib
96.0
(48.1 to 96.5)
95.3
(94.3 to 96.0)
Regorafenib metabolites M-2
96.0
(48.1 to 96.5)
95.3
(94.3 to 96.0)
Regorafenib metabolites M-5
96.0
(48.1 to 96.5)
95.3
(94.3 to 96.0)
16.Secondary Outcome
Title RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation. Accumulation ratio based on maximum plasma concentration (Cmax) was calculated as ratio of Cmax,md and Cmax.
Time Frame Up to 25 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 13 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Accumulation Ratio
Regorafenib
1.51
(60.0%)
1.96
(68.2%)
Regorafenib metabolites M-2
3.83
(44.9%)
5.94
(216%)
Regorafenib metabolites M-5
39.7
(94.0%)
81.8
(515%)
17.Secondary Outcome
Title RAAUC (Accumulation Ratio Calculated From AUC(0-24)md and AUC(0-24)) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation. RAAUC calculated as ratio of AUC(0-24)md and AUC(0-24).
Time Frame Up to 25 days
Hide Outcome Measure Data
Hide Analysis Population Description
In Normal/mild renal impairment group, participants analyzed for regorafenib, M-2 and M-5 are n=13, 13 and 12 respectively. In Severe renal impairment group, participants analyzed for regorafenib, M-2 and M-5 are n=4, 4 and 3 respectively. Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 18 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Accumulation Ratio
Regorafenib
1.97
(57.1%)
1.96
(52.0%)
Regorafenib metabolites M-2
4.32
(45.0%)
6.00
(172%)
Regorafenib metabolites M-5
48.3
(76.0%)
87.0
(585%)
18.Secondary Outcome
Title RLin (Linearity Factor Calculated as Ratio From AUC(0-24)md and AUC) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Hide Description Based on non-compartmental PK evaluation. RLin is the linearity factor of PK after multiple administrations of identical doses calculated as ratio of AUC(0-24)md and AUC.
Time Frame Up to 25 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 9 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Linearity factor calculated as ratio
Regorafenib (n=5, 2)
0.957
(49.2%)
0.469
(5.24%)
Regorafenib metabolites M-2 (n= 9, 2)
1.98
(40.7%)
1.19
(144%)
Regorafenib metabolites M-5 (n=0, 0)
NA [1] 
(NA%)
NA [1] 
(NA%)
[1]
Number of analyzed subjects is zero.
19.Secondary Outcome
Title AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8
Hide Description based on non-compartmental PK evaluation
Time Frame Days 21-22: 0-24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 12 4
Mean (Standard Deviation)
Unit of Measure: percentage of dose
Regorafenib metabolites M-7 5.094  (2.322) 1.647  (0.753)
Regorafenib metabolites M-8 2.566  (1.561) 1.238  (0.684)
20.Secondary Outcome
Title AE,ur(0-10) Stage 1 (Amount of Drug Excreted Via Urine During the Collection Interval 0-10 Hours Post Administration) for Metabolites M-7 and M-8
Hide Description based on non-compartmental PK evaluation
Time Frame Days 1-2: 0-10 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 14 5
Mean (Standard Deviation)
Unit of Measure: percentage of dose
Regorafenib metabolites M-7 1.752  (0.611) 0.449  (0.301)
Regorafenib metabolites M-8 0.486  (0.382) 0.053  (0.089)
21.Secondary Outcome
Title AE,ur(10-24) Stage 1 ((Amount of Drug Excreted Via Urine During the Collection Interval 10-24 Hours Post Administration) for Metabolites M-7 and M-8
Hide Description based on non-compartmental PK evaluation
Time Frame Days 1-2: 10-24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 14 6
Mean (Standard Deviation)
Unit of Measure: percentage of dose
Regorafenib metabolites M-7 1.855  (0.629) 0.746  (0.441)
Regorafenib metabolites M-8 0.634  (0.374) 0.117  (0.133)
22.Secondary Outcome
Title AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8
Hide Description based on non-compartmental PK evaluation
Time Frame Days 21-22: 0-10 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 12 4
Mean (Standard Deviation)
Unit of Measure: percentage of dose
Regorafenib metabolites M-7 2.655  (1.346) 0.600  (0.255)
Regorafenib metabolites M-8 1.292  (0.902) 0.469  (0.338)
23.Secondary Outcome
Title AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8
Hide Description based on non-compartmental PK evaluation
Time Frame Days 21-22: 10-24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 12 4
Mean (Standard Deviation)
Unit of Measure: percentage of dose
Regorafenib metabolites M-7 2.440  (1.098) 1.047  (0.738)
Regorafenib metabolites M-8 1.274  (0.712) 0.769  (0.497)
24.Other Pre-specified Outcome
Title Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors)
Hide Description Positron emission tomography - computed tomography (ET-CT), CT, or magnetic resonance imaging (MRI) scans of all anatomic regions involved with the disease were performed to assess tumor response using the Response Evaluation Criteria in Solid Tumors, Version 1.1. (RECIST v1.1). Bone metastases were assessed by bone scintigraphy (bone scan). Tumor measurements and evaluation of tumor response were performed at baseline and within the last 7 days of Cycle 2. Thereafter, if subjects continued regorafenib treatment, tumor assessments were performed after every third cycle and at the end-of-treatment (EOT) visit. In addition, outcome of "Assessment of Bone Metastases by Scintigraphy if Applicable (Bone Scan)" was registered, the results of which has been reported as tumor response in this outcome as well.
Time Frame Up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Normal/mild renal impairment group had only tumor assessments at screening, thus excluded from efficacy analysis.
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description:
Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
Overall Number of Participants Analyzed 15 6
Measure Type: Number
Unit of Measure: participants
Complete response (CR) 0 0
Partial response (PR) 0 0
Stable disease (SD) 10 5
Non CR/Non PD 0 0
Progressive disease (PD) 5 1
Not evaluable 0 0
Time Frame From start of study treatment until 30 days after last dose of study medication.
Adverse Event Reporting Description Safety was assessed routinely and on an ongoing basis
 
Arm/Group Title Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Hide Arm/Group Description Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days.
All-Cause Mortality
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/18 (50.00%)      2/6 (33.33%)    
Cardiac disorders     
Stress cardiomyopathy  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Gastrointestinal disorders     
Intestinal obstruction  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Pancreatitis  1  1/18 (5.56%)  3 0/6 (0.00%)  0
Small intestinal obstruction  1  2/18 (11.11%)  4 0/6 (0.00%)  0
General disorders     
Chest pain  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Metabolism and nutrition disorders     
Dehydration  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  1/18 (5.56%)  1 1/6 (16.67%)  1
Renal and urinary disorders     
Haematuria  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pleural effusion  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Embolism  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI-CTCAE (4.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/18 (100.00%)      6/6 (100.00%)    
Blood and lymphatic system disorders     
Anaemia  1  2/18 (11.11%)  6 2/6 (33.33%)  5
Neutropenia  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Thrombocytopenia  1  1/18 (5.56%)  1 2/6 (33.33%)  3
Cardiac disorders     
Angina pectoris  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Tachycardia  1  2/18 (11.11%)  2 0/6 (0.00%)  0
Ear and labyrinth disorders     
Ear discomfort  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Eye disorders     
Cataract  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Chalazion  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Eye pain  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Glaucoma  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Vision blurred  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Gastrointestinal disorders     
Abdominal discomfort  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Abdominal distension  1  1/18 (5.56%)  1 1/6 (16.67%)  1
Abdominal pain  1  5/18 (27.78%)  12 3/6 (50.00%)  6
Abdominal pain lower  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Abdominal pain upper  1  1/18 (5.56%)  1 1/6 (16.67%)  1
Cheilitis  1  1/18 (5.56%)  1 3/6 (50.00%)  3
Constipation  1  5/18 (27.78%)  7 3/6 (50.00%)  4
Diarrhoea  1  8/18 (44.44%)  16 4/6 (66.67%)  12
Diverticulum  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Dry mouth  1  2/18 (11.11%)  2 2/6 (33.33%)  3
Dyspepsia  1  4/18 (22.22%)  6 1/6 (16.67%)  1
Eructation  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Faecal incontinence  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Faecaloma  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Flatulence  1  2/18 (11.11%)  3 0/6 (0.00%)  0
Gastrointestinal pain  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Gastrooesophageal reflux disease  1  3/18 (16.67%)  4 1/6 (16.67%)  1
Glossodynia  1  1/18 (5.56%)  1 1/6 (16.67%)  2
Haematemesis  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Inguinal hernia  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Lip ulceration  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Nausea  1  10/18 (55.56%)  20 6/6 (100.00%)  8
Odynophagia  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Proctalgia  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Retching  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Stomatitis  1  3/18 (16.67%)  6 2/6 (33.33%)  8
Toothache  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Vomiting  1  6/18 (33.33%)  8 4/6 (66.67%)  9
General disorders     
Asthenia  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Chest pain  1  3/18 (16.67%)  3 0/6 (0.00%)  0
Chills  1  2/18 (11.11%)  2 2/6 (33.33%)  2
Drug intolerance  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Early satiety  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Fatigue  1  13/18 (72.22%)  24 3/6 (50.00%)  7
Impaired healing  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Medical device site reaction  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Mucosal inflammation  1  4/18 (22.22%)  14 1/6 (16.67%)  1
Oedema  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Oedema peripheral  1  2/18 (11.11%)  2 0/6 (0.00%)  0
Pyrexia  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Vessel puncture site bruise  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Infections and infestations     
Candida infection  1  3/18 (16.67%)  4 0/6 (0.00%)  0
Cellulitis  1  2/18 (11.11%)  2 0/6 (0.00%)  0
Eye infection  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Pneumonia  1  2/18 (11.11%)  2 0/6 (0.00%)  0
Sinusitis  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Subcutaneous abscess  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Urinary tract infection  1  1/18 (5.56%)  1 1/6 (16.67%)  1
Injury, poisoning and procedural complications     
Ankle fracture  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Arthropod bite  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Contusion  1  2/18 (11.11%)  2 1/6 (16.67%)  1
Face injury  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Fall  1  1/18 (5.56%)  1 1/6 (16.67%)  1
Procedural site reaction  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Subcutaneous haematoma  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  2/18 (11.11%)  2 1/6 (16.67%)  2
Amylase increased  1  0/18 (0.00%)  0 1/6 (16.67%)  8
Aspartate aminotransferase increased  1  1/18 (5.56%)  3 1/6 (16.67%)  2
Blood bilirubin increased  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Blood creatinine increased  1  2/18 (11.11%)  3 2/6 (33.33%)  4
Blood fibrinogen decreased  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Blood urea increased  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Cardiac murmur  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Haemoglobin decreased  1  0/18 (0.00%)  0 2/6 (33.33%)  2
International normalised ratio increased  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Lipase increased  1  0/18 (0.00%)  0 1/6 (16.67%)  10
Troponin increased  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Weight decreased  1  6/18 (33.33%)  9 1/6 (16.67%)  3
Metabolism and nutrition disorders     
Decreased appetite  1  11/18 (61.11%)  23 3/6 (50.00%)  5
Dehydration  1  3/18 (16.67%)  4 0/6 (0.00%)  0
Hyperglycaemia  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Hyperlipasaemia  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Hyperuricaemia  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Hypocalcaemia  1  0/18 (0.00%)  0 1/6 (16.67%)  3
Hypoglycaemia  1  0/18 (0.00%)  0 1/6 (16.67%)  2
Hypokalaemia  1  1/18 (5.56%)  3 0/6 (0.00%)  0
Hypomagnesaemia  1  2/18 (11.11%)  2 1/6 (16.67%)  4
Hyponatraemia  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Hypophosphataemia  1  1/18 (5.56%)  3 1/6 (16.67%)  1
Lactose intolerance  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  5/18 (27.78%)  15 3/6 (50.00%)  4
Back pain  1  4/18 (22.22%)  6 2/6 (33.33%)  3
Muscle spasms  1  6/18 (33.33%)  14 0/6 (0.00%)  0
Muscular weakness  1  2/18 (11.11%)  6 0/6 (0.00%)  0
Musculoskeletal chest pain  1  2/18 (11.11%)  3 0/6 (0.00%)  0
Musculoskeletal discomfort  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Musculoskeletal pain  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Musculoskeletal stiffness  1  2/18 (11.11%)  2 0/6 (0.00%)  0
Myalgia  1  6/18 (33.33%)  15 2/6 (33.33%)  3
Neck mass  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Neck pain  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Pain in extremity  1  1/18 (5.56%)  5 0/6 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Nervous system disorders     
Disturbance in attention  1  2/18 (11.11%)  2 0/6 (0.00%)  0
Dizziness  1  4/18 (22.22%)  4 2/6 (33.33%)  2
Dysgeusia  1  3/18 (16.67%)  4 0/6 (0.00%)  0
Headache  1  10/18 (55.56%)  18 2/6 (33.33%)  5
Neuropathy peripheral  1  2/18 (11.11%)  7 0/6 (0.00%)  0
Paraesthesia  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Peripheral sensory neuropathy  1  2/18 (11.11%)  2 0/6 (0.00%)  0
Sensory disturbance  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Psychiatric disorders     
Agitation  1  1/18 (5.56%)  3 0/6 (0.00%)  0
Anxiety  1  1/18 (5.56%)  3 0/6 (0.00%)  0
Insomnia  1  3/18 (16.67%)  3 1/6 (16.67%)  1
Renal and urinary disorders     
Dysuria  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Proteinuria  1  1/18 (5.56%)  1 3/6 (50.00%)  6
Urinary retention  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Reproductive system and breast disorders     
Dysmenorrhoea  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Menstruation irregular  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Pelvic pain  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/18 (22.22%)  5 1/6 (16.67%)  1
Dysphonia  1  8/18 (44.44%)  12 2/6 (33.33%)  9
Dyspnoea  1  6/18 (33.33%)  8 1/6 (16.67%)  1
Dyspnoea exertional  1  1/18 (5.56%)  1 2/6 (33.33%)  2
Epistaxis  1  2/18 (11.11%)  2 1/6 (16.67%)  1
Haemoptysis  1  3/18 (16.67%)  3 0/6 (0.00%)  0
Hiccups  1  0/18 (0.00%)  0 2/6 (33.33%)  2
Nasal congestion  1  1/18 (5.56%)  7 0/6 (0.00%)  0
Oropharyngeal pain  1  2/18 (11.11%)  2 1/6 (16.67%)  1
Productive cough  1  1/18 (5.56%)  3 0/6 (0.00%)  0
Rhinorrhoea  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Skin and subcutaneous tissue disorders     
Alopecia  1  4/18 (22.22%)  7 0/6 (0.00%)  0
Decubitus ulcer  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Dry skin  1  2/18 (11.11%)  2 1/6 (16.67%)  1
Eczema  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Erythema  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Hyperhidrosis  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Nail disorder  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Night sweats  1  1/18 (5.56%)  1 1/6 (16.67%)  1
Pain of skin  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Palmar erythema  1  1/18 (5.56%)  2 0/6 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome  1  10/18 (55.56%)  32 3/6 (50.00%)  15
Pruritus  1  2/18 (11.11%)  3 1/6 (16.67%)  1
Rash  1  5/18 (27.78%)  12 2/6 (33.33%)  3
Rash maculo-papular  1  1/18 (5.56%)  1 1/6 (16.67%)  2
Skin hyperpigmentation  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Skin lesion  1  0/18 (0.00%)  0 1/6 (16.67%)  1
Swelling face  1  1/18 (5.56%)  1 0/6 (0.00%)  0
Vascular disorders     
Flushing  1  1/18 (5.56%)  1 1/6 (16.67%)  1
Hot flush  1  2/18 (11.11%)  2 0/6 (0.00%)  0
Hypertension  1  8/18 (44.44%)  10 4/6 (66.67%)  10
Hypotension  1  2/18 (11.11%)  2 1/6 (16.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI-CTCAE (4.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Therapeutic Area Head
Organization: Bayer AG
EMail: clinical-trials-contact@bayer.com
Layout table for additonal information
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01853046    
Other Study ID Numbers: 16653
First Submitted: May 10, 2013
First Posted: May 14, 2013
Results First Submitted: July 12, 2016
Results First Posted: February 20, 2017
Last Update Posted: February 20, 2017