Neoplasms
Conditions
Keywords
Regorafenib, pharmacokinetics, safety, severe renal impairment, Solid tumors
Brief summary
To characterize the pharmacokinetics and safety of regorafenib in cancer subjects with severe renal impairment when compared to the Control group (cancer subjects with normal or mildly impaired renal function)
Interventions
DRUGRegorafenib (Stivarga, BAY73-4506)
Regorafenib 160 mg o.d. will be administered as a single dose on Day 1 of Stage 1 followed by multiple dosing in an intermittent administration schedule (3 week-on/1 week-off) over 2 cycles in Stage 2 (56 days, cycle defined as 28 days)
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with histologically confirmed, locally advanced or metastatic, refractory solid tumors who are not candidates for standard therapy * Male or female subject ≥ 18 years of age * Women of childbearing potential must have a negative urine pregnancy test performed within 7 days before start of study treatment * Life expectancy at least 8 weeks * Adequate bone marrow, and liver function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2 * For subjects with NORMAL OR MILDLY IMPAIRED RENAL FUNCTION (Control group); to be tested within 7 days of starting the study treatment: * Estimated creatinine clearance (CLcr) ≥ 60 mL/min as calculated using the Cockcroft-Gault equation * For subjects with SEVERELY IMPAIRED renal function; to be tested within 7 days of starting the study treatment: * CLcr 15-29 mL/min as calculated using the Cockcroft-Gault equation
Exclusion criteria
* Symptomatic metastatic brain or meningeal tumors * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication * History of organ allograft * Non-healing wound, skin ulcer, or bone fracture * Pheochromocytoma * Uncontrolled concurrent medical illness including uncontrolled hypertension * History of cardiac disease * Pleural effusion or ascites that causes respiratory compromise * Interstitial lung disease with ongoing signs and symptoms at the time of screening * Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication * Subjects with evidence or history of bleeding diathesis; any hemorrhage or bleeding event NCI-CTCAE Grade ≥ 3 or higher within 4 weeks of start of investigational treatment * Dehydration NCI-CTCAEversion 4.0 Grade ≥ 1 * Unresolved toxicity higher than NCI-CTCAE version 4.0 Grade 1 attributed to any prior therapy/procedure (excluding alopecia or anemia or grade 2 neuropathy that is not reversible due to oxaliplatin) * Seizure disorder requiring anticonvulsant therapy (such as steroids or anti-epileptics) * For subjects with SEVERELY IMPAIRED renal function: * Renal failure requiring hemo- or peritoneal dialysis * Acute renal failure * Acute nephritis * Nephrotic syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Days 1-2: 0-24 hours | Amount of drug excreted into urine during the collection interval 0-24 hours post dose was expressed as percentage of administered dose. |
| 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 | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose | 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. |
| Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | 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. |
| 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 | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | 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. |
| Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | based on non-compartmental PK evaluation. |
| 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 | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | 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. |
| 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 | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | 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. |
| 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 | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | 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. |
| AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose | Based on non-compartmental PK evaluation. |
| Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | 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. |
| AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | based on non-compartmental PK evaluation. |
| Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | based on non-compartmental PK evaluation |
| RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Up to 25 days | Based on non-compartmental PK evaluation. Accumulation ratio based on maximum plasma concentration (Cmax) was calculated as ratio of Cmax,md and Cmax. |
| 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 | Up to 25 days | Based on non-compartmental PK evaluation. RAAUC calculated as ratio of AUC(0-24)md and AUC(0-24). |
| 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 | Up to 25 days | 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. |
| AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8 | Days 21-22: 0-24 hours | based on non-compartmental PK evaluation |
| 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 | Days 1-2: 0-10 hours | based on non-compartmental PK evaluation |
| 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 | Days 1-2: 10-24 hours | based on non-compartmental PK evaluation |
| AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8 | Days 21-22: 0-10 hours | based on non-compartmental PK evaluation |
| AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8 | Days 21-22: 10-24 hours | based on non-compartmental PK evaluation |
| 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 | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | based on non-compartmental PK evaluation |
| 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 | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Up to 6 months | 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. |
Countries
Canada, United States
Participant flow
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
Participants by arm
| Arm | Count |
|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment 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. | 18 |
| Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment 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. | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 2 |
| Overall Study | Disease progression | 13 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment | Total |
|---|---|---|---|
| Age, Continuous | 62.0 years STANDARD_DEVIATION 9.6 | 64.2 years STANDARD_DEVIATION 6.9 | 62.5 years STANDARD_DEVIATION 8.9 |
| Gender Female | 9 Participants | 4 Participants | 13 Participants |
| Gender Male | 9 Participants | 2 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 18 | 6 / 6 |
| serious Total, serious adverse events | 9 / 18 | 2 / 6 |
Outcome results
Primary
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
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-7 | 3.607 percentage of dose | Standard Deviation 1.124 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-8 | 1.120 percentage of dose | Standard Deviation 0.737 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-7 | 1.309 percentage of dose | Standard Deviation 0.649 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-8 | 0.184 percentage of dose | Standard Deviation 0.229 |
Primary
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
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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib | 67.2 mg*h/L | Geometric Coefficient of Variation 45.5 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 | 27.8 mg*h/L | Geometric Coefficient of Variation 80.4 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 | 5.25 mg*h/L | Geometric Coefficient of Variation 145 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib | 76.6 mg*h/L | Geometric Coefficient of Variation 50.3 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 | 2.34 mg*h/L | Geometric Coefficient of Variation 79.8 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 | 19.0 mg*h/L | Geometric Coefficient of Variation 58.7 |
Comparison: 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.90% CI: [0.796, 1.63]
Comparison: 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.90% CI: [0.397, 1.18]
Comparison: 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 ANOVAs90% CI: [0.2, 0.996]
Secondary
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
based on non-compartmental PK evaluation
Time frame: Days 1-2: 0-10 hours
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-7 | 1.752 percentage of dose | Standard Deviation 0.611 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-8 | 0.486 percentage of dose | Standard Deviation 0.382 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-7 | 0.449 percentage of dose | Standard Deviation 0.301 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-8 | 0.053 percentage of dose | Standard Deviation 0.089 |
Secondary
AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8
based on non-compartmental PK evaluation
Time frame: Days 21-22: 0-10 hours
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8 | Regorafenib metabolites M-7 | 2.655 percentage of dose | Standard Deviation 1.346 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8 | Regorafenib metabolites M-8 | 1.292 percentage of dose | Standard Deviation 0.902 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8 | Regorafenib metabolites M-7 | 0.600 percentage of dose | Standard Deviation 0.255 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8 | Regorafenib metabolites M-8 | 0.469 percentage of dose | Standard Deviation 0.338 |
Secondary
AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8
based on non-compartmental PK evaluation
Time frame: Days 21-22: 0-24 hours
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8 | Regorafenib metabolites M-7 | 5.094 percentage of dose | Standard Deviation 2.322 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8 | Regorafenib metabolites M-8 | 2.566 percentage of dose | Standard Deviation 1.561 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8 | Regorafenib metabolites M-7 | 1.647 percentage of dose | Standard Deviation 0.753 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8 | Regorafenib metabolites M-8 | 1.238 percentage of dose | Standard Deviation 0.684 |
Secondary
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
based on non-compartmental PK evaluation
Time frame: Days 1-2: 10-24 hours
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-7 | 1.855 percentage of dose | Standard Deviation 0.629 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-8 | 0.634 percentage of dose | Standard Deviation 0.374 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-7 | 0.746 percentage of dose | Standard Deviation 0.441 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-8 | 0.117 percentage of dose | Standard Deviation 0.133 |
Secondary
AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8
based on non-compartmental PK evaluation
Time frame: Days 21-22: 10-24 hours
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8 | Regorafenib metabolites M-7 | 2.440 percentage of dose | Standard Deviation 1.098 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8 | Regorafenib metabolites M-8 | 1.274 percentage of dose | Standard Deviation 0.712 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8 | Regorafenib metabolites M-7 | 1.047 percentage of dose | Standard Deviation 0.738 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8 | Regorafenib metabolites M-8 | 0.769 percentage of dose | Standard Deviation 0.497 |
Secondary
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
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib | 30.0 mg*h/L | Geometric Coefficient of Variation 39.8 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 | 1.17 mg*h/L | Geometric Coefficient of Variation 116 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 | 13.5 mg*h/L | Geometric Coefficient of Variation 70 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib | 28.4 mg*h/L | Geometric Coefficient of Variation 62 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 | 7.93 mg*h/L | Geometric Coefficient of Variation 72.7 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 | 0.474 mg*h/L | Geometric Coefficient of Variation 101 |
Secondary
AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 56.0 mg*h/L | Geometric Coefficient of Variation 56.4 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 53.9 mg*h/L | Geometric Coefficient of Variation 63.1 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 49.7 mg*h/L | Geometric Coefficient of Variation 130 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 45.2 mg*h/L | Geometric Coefficient of Variation 45.8 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 35.0 mg*h/L | Geometric Coefficient of Variation 207 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 34.2 mg*h/L | Geometric Coefficient of Variation 438 |
Secondary
AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 133 mg*h/L | Geometric Coefficient of Variation 55.1 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 136 mg*h/L | Geometric Coefficient of Variation 64.9 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 183 mg*h/L | Geometric Coefficient of Variation 128 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 111 mg*h/L | Geometric Coefficient of Variation 54.8 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 92.3 mg*h/L | Geometric Coefficient of Variation 280 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 134 mg*h/L | Geometric Coefficient of Variation 459 |
Secondary
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
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib (n=6, 3) | 59.5 mg*h/L | Geometric Coefficient of Variation 26.1 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 (n=13, 4) | 32.6 mg*h/L | Geometric Coefficient of Variation 89 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA mg*h/L | — |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib (n=6, 3) | 98.7 mg*h/L | Geometric Coefficient of Variation 71 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 (n=13, 4) | 20.8 mg*h/L | Geometric Coefficient of Variation 65.4 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA mg*h/L | — |
Secondary
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
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib (n=6, 3) | 2.69 L/H | Geometric Coefficient of Variation 26.1 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 (n=13, 4) | 5.08 L/H | Geometric Coefficient of Variation 89 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA L/H | — |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib (n=6, 3) | 1.62 L/H | Geometric Coefficient of Variation 71 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 (n=13, 4) | 7.95 L/H | Geometric Coefficient of Variation 65.4 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA L/H | — |
Secondary
Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 2.45 mg/L | Geometric Coefficient of Variation 47 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 1.01 mg/L | Geometric Coefficient of Variation 66.7 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 0.0877 mg/L | Geometric Coefficient of Variation 125 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 2.00 mg/L | Geometric Coefficient of Variation 69.7 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 0.525 mg/L | Geometric Coefficient of Variation 69.6 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 0.0341 mg/L | Geometric Coefficient of Variation 67 |
Secondary
Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 3.52 mg/L | Geometric Coefficient of Variation 54.9 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 3.52 mg/L | Geometric Coefficient of Variation 58.8 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 3.25 mg/L | Geometric Coefficient of Variation 133 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 2.87 mg/L | Geometric Coefficient of Variation 62.2 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 2.29 mg/L | Geometric Coefficient of Variation 257 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 2.23 mg/L | Geometric Coefficient of Variation 659 |
Secondary
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
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
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib | 1.97 Accumulation Ratio | Geometric Coefficient of Variation 57.1 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 | 4.32 Accumulation Ratio | Geometric Coefficient of Variation 45 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 | 48.3 Accumulation Ratio | Geometric Coefficient of Variation 76 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib | 1.96 Accumulation Ratio | Geometric Coefficient of Variation 52 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 | 6.00 Accumulation Ratio | Geometric Coefficient of Variation 172 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 | 87.0 Accumulation Ratio | Geometric Coefficient of Variation 585 |
Secondary
RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 1.51 Accumulation Ratio | Geometric Coefficient of Variation 60 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 3.83 Accumulation Ratio | Geometric Coefficient of Variation 44.9 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 39.7 Accumulation Ratio | Geometric Coefficient of Variation 94 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 1.96 Accumulation Ratio | Geometric Coefficient of Variation 68.2 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 5.94 Accumulation Ratio | Geometric Coefficient of Variation 216 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 81.8 Accumulation Ratio | Geometric Coefficient of Variation 515 |
Secondary
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
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib (n=5, 2) | 0.957 Linearity factor calculated as ratio | Geometric Coefficient of Variation 49.2 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 (n= 9, 2) | 1.98 Linearity factor calculated as ratio | Geometric Coefficient of Variation 40.7 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA Linearity factor calculated as ratio | — |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib (n=5, 2) | 0.469 Linearity factor calculated as ratio | Geometric Coefficient of Variation 5.24 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 (n= 9, 2) | 1.19 Linearity factor calculated as ratio | Geometric Coefficient of Variation 144 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA Linearity factor calculated as ratio | — |
Secondary
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
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib (n=6, 3) | 28.7 h | Geometric Coefficient of Variation 23 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 (n=13, 4) | 26.2 h | Geometric Coefficient of Variation 25.7 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA h | — |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA h | — |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib (n=6, 3) | 27.9 h | Geometric Coefficient of Variation 32 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 (n=13, 4) | 25.5 h | Geometric Coefficient of Variation 24 |
Secondary
Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 96.0 h |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 96.0 h |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 96.0 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 95.3 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 95.3 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 95.3 h |
Secondary
Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 95.7 h |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 95.7 h |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 95.7 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib | 95.8 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-2 | 95.8 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 | Regorafenib metabolites M-5 | 95.8 h |
Secondary
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
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib | 3.97 h |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 | 4.12 h |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 | 0.000 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib | 4.25 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 | 4.00 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 | 0.000 h |
Secondary
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
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib | 4.03 h |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 | 4.03 h |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 | 47.8 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib | 3.04 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 | 6.04 h |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 | 48.9 h |
Secondary
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
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
Population: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib (n=6, 3) | 111 L | Geometric Coefficient of Variation 31.9 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-2 (n=13, 4) | 192 L | Geometric Coefficient of Variation 83.8 |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA L | — |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib (n=6, 3) | 65.2 L | Geometric Coefficient of Variation 81 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-2 (n=13, 4) | 292 L | Geometric Coefficient of Variation 71.1 |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | 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 | Regorafenib metabolites M-5 (n=0, 0) | NA L | — |
Other Pre-specified
Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors)
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
Population: Participants in the Normal/mild renal impairment group had only tumor assessments at screening, thus excluded from efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Stable disease (SD) | 10 participants |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Complete response (CR) | 0 participants |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Partial response (PR) | 0 participants |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Non CR/Non PD | 0 participants |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Progressive disease (PD) | 5 participants |
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Not evaluable | 0 participants |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Progressive disease (PD) | 1 participants |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Non CR/Non PD | 0 participants |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Complete response (CR) | 0 participants |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Not evaluable | 0 participants |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Partial response (PR) | 0 participants |
| Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) | Stable disease (SD) | 5 participants |