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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)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Experimental | 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. |
|
| Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Regorafenib (Stivarga, BAY73-4506) | Drug | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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. | Days 1-2: 0-24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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:
For subjects with SEVERELY IMPAIRED renal function; to be tested within 7 days of starting the study treatment:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Bayer Study Director | Bayer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Los Angeles | California | 90033 | United States | |||
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
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg*h/L | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
|
From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stress cardiomyopathy | Cardiac disorders | NCI-CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Therapeutic Area Head | Bayer AG | clinical-trials-contact@bayer.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| C559147 | regorafenib |
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| 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. | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose |
| 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. | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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. | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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. | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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. | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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. | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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. | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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. | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose |
| 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. | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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. | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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 | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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 | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
| 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. | Up to 25 days |
| 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). | Up to 25 days |
| 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. | Up to 25 days |
| 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 | Days 21-22: 0-24 hours |
| 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 | Days 1-2: 0-10 hours |
| 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 | Days 1-2: 10-24 hours |
| AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8 | based on non-compartmental PK evaluation | Days 21-22: 0-10 hours |
| AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8 | based on non-compartmental PK evaluation | Days 21-22: 10-24 hours |
| Up to 6 months |
| Aurora |
| Colorado |
| 80045 |
| United States |
| St Louis | Missouri | 63110 | United States |
| Lebanon | New Hampshire | 03756 | United States |
| Buffalo | New York | 14263-0001 | United States |
| Edmonton | Alberta | T6G 1Z2 | Canada |
| Vancouver | British Columbia | V5Z 4E6 | Canada |
| Hamilton | Ontario | L8V 5C2 | Canada |
| Montreal | Quebec | H2L 4M1 | Canada |
| Disease progression |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Gender | Count of Participants | Participants |
|
| OG001 | 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. |
|
|
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| 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. | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Mean | Standard Deviation | percentage of dose | Days 1-2: 0-24 hours |
|
|
|
| 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. | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg*h/L | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
|
|
|
| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg*h/L | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose |
|
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| 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg/L | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
|
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| 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. | Posted | Median | Full Range | h | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
|
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| 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. | Posted | Median | Full Range | h | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
|
|
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| 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. | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
|
|
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| 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. | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/H | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
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| 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. | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg*h/L | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose |
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| 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. | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg/L | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
|
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| 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. | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | mg*h/L | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
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| 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 | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Median | Full Range | h | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
|
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| 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 | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Median | Full Range | h | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
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| 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. | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | Accumulation Ratio | Up to 25 days |
|
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| 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). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | Accumulation Ratio | Up to 25 days |
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|
|
| 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. | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Geometric Mean | Geometric Coefficient of Variation | Linearity factor calculated as ratio | Up to 25 days |
|
|
|
| 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 | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Mean | Standard Deviation | percentage of dose | Days 21-22: 0-24 hours |
|
|
|
| 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 | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Mean | Standard Deviation | percentage of dose | Days 1-2: 0-10 hours |
|
|
|
| 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 | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Mean | Standard Deviation | percentage of dose | Days 1-2: 10-24 hours |
|
|
|
| Secondary | AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8 | based on non-compartmental PK evaluation | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Mean | Standard Deviation | percentage of dose | Days 21-22: 0-10 hours |
|
|
|
| Secondary | AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8 | based on non-compartmental PK evaluation | Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. | Posted | Mean | Standard Deviation | percentage of dose | Days 21-22: 10-24 hours |
|
|
|
| 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. | Participants in the Normal/mild renal impairment group had only tumor assessments at screening, thus excluded from efficacy analysis. | Posted | Number | participants | Up to 6 months |
|
|
|
| 9 |
| 18 |
| 18 |
| 18 |
| EG001 | 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. | 2 | 6 | 6 | 6 |
| Intestinal obstruction | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Chest pain | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Embolism | Vascular disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Ear discomfort | Ear and labyrinth disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Cataract | Eye disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Chalazion | Eye disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Eye pain | Eye disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Glaucoma | Eye disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Vision blurred | Eye disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Abdominal pain lower | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Diverticulum | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Faecal incontinence | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Faecaloma | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Glossodynia | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Lip ulceration | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Odynophagia | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Retching | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Asthenia | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Chest pain | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Chills | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Drug intolerance | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Early satiety | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Impaired healing | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Medical device site reaction | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Mucosal inflammation | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Oedema | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Pyrexia | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Vessel puncture site bruise | General disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Candida infection | Infections and infestations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Eye infection | Infections and infestations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Subcutaneous abscess | Infections and infestations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Face injury | Injury, poisoning and procedural complications | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Procedural site reaction | Injury, poisoning and procedural complications | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Subcutaneous haematoma | Injury, poisoning and procedural complications | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Amylase increased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Blood creatinine increased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Blood fibrinogen decreased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Blood urea increased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Cardiac murmur | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| International normalised ratio increased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Lipase increased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Troponin increased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Weight decreased | Investigations | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hyperlipasaemia | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Lactose intolerance | Metabolism and nutrition disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Neck mass | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Sensory disturbance | Nervous system disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Menstruation irregular | Reproductive system and breast disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Palmar erythema | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hot flush | Vascular disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | NCI-CTCAE (4.0) | Systematic Assessment |
|
Not provided
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| Regorafenib metabolites M-5 (n=0, 0) |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 (n=0, 0) |
|
| Regorafenib metabolites M-5 (n=0, 0) |
|
| Regorafenib metabolites M-5 (n=0, 0) |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 |
|
| Regorafenib metabolites M-5 (n=0, 0) |
|
| Stable disease (SD) |
|
| Non CR/Non PD |
|
| Progressive disease (PD) |
|
| Not evaluable |
|