Pharmacokinetics and Safety of Regorafenib (BAY73-4506) in Cancer Subjects With Severe Renal Impairment
Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT01853046
Collaborator
(none)
24
9
2
29
2.7
0.1
Study Details
Study Description
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
24 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I, Multi-center, Non-randomized, Open Label, Parallel-group Study Evaluating the Pharmacokinetics and Safety of Regorafenib (BAY73-4506) in Cancer Subjects With Severe Renal Impairment Compared to a Control Group
Study Start Date
:
Jun 1, 2013
Actual Primary Completion Date
:
Jul 1, 2015
Actual Study Completion Date
:
Nov 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Regorafenib (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)
|
| Experimental: 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. |
Drug: Regorafenib (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)
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
Secondary Outcome Measures
- 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.
- 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.
- 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
- 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
Other Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Los Angeles | California | United States | 90033 | |
| 2 | Aurora | Colorado | United States | 80045 | |
| 3 | St. Louis | Missouri | United States | 63110 | |
| 4 | Lebanon | New Hampshire | United States | 03756 | |
| 5 | Buffalo | New York | United States | 14263-0001 | |
| 6 | Edmonton | Alberta | Canada | T6G 1Z2 | |
| 7 | Vancouver | British Columbia | Canada | V5Z 4E6 | |
| 8 | Hamilton | Ontario | Canada | L8V 5C2 | |
| 9 | Montreal | Quebec | Canada | H2L 4M1 |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01853046
Other Study ID Numbers:
- 16653
First Posted:
May 14, 2013
Last Update Posted:
Feb 20, 2017
Last Verified:
Dec 1, 2016
Keywords provided by Bayer
Additional relevant MeSH terms:
Study Results
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 Detail | 15 participants (38.5% of 39) were screening failures and 24 participants received treatment with regorafenib. All 15 participants who failed to meet the inclusion and / or exclusion criteria were not assigned to study |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Period Title: Overall Study | ||
| STARTED | 18 | 6 |
| Received Treatment | 18 | 6 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 18 | 6 |
Baseline Characteristics
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib (Stivarga, BAY73-4506)-Severe Renal Impairment | Total |
|---|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Total of all reporting groups |
| Overall Participants | 18 | 6 | 24 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
62.0
(9.6)
|
64.2
(6.9)
|
62.5
(8.9)
|
| Gender (Count of Participants) | |||
| Female |
9
50%
|
4
66.7%
|
13
54.2%
|
| Male |
9
50%
|
2
33.3%
|
11
45.8%
|
Outcome Measures
| Title | AUC(0-tlast) [Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point >LLOQ (Lower Limit of Quantification)] for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation. The AUC(0-tlast) [Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point >LLOQ (Lower Limit of Quantification)] is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. |
| Time Frame | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib |
67.2
(45.5)
|
76.6
(50.3)
|
| Regorafenib metabolites M-2 |
27.8
(80.4)
|
19.0
(58.7)
|
| Regorafenib metabolites M-5 |
5.25
(145)
|
2.34
(79.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment, Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Comments | Point estimates (LS-means) and 2-sided exploratory 90% confidence intervals for AUC(0-tlast) of regorafenib calculated by re-transformation of the logarithmic data from ANOVAs. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean |
| Estimated Value | 1.14 | |
| Confidence Interval |
(2-Sided) 90% 0.796 to 1.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment, Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Comments | Point estimates (LS-means) and 2-sided exploratory 90% confidence intervals for AUC(0-tlast) of metabolites M-2 calculated by re-transformation of the logarithmic data from ANOVAs. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS-means |
| Estimated Value | 0.684 | |
| Confidence Interval |
(2-Sided) 90% 0.397 to 1.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment, Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Comments | Point estimates (LS-means) and 2-sided exploratory 90% confidence intervals for AUC(0-tlast) of metabolites M-5 calculated by re-transformation of the logarithmic data from ANOVAs | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS-means |
| Estimated Value | 0.446 | |
| Confidence Interval |
(2-Sided) 90% 0.200 to 0.996 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0-24 Hours Post Administration) for Metabolites M-7 and M-8 |
|---|---|
| Description | Amount of drug excreted into urine during the collection interval 0-24 hours post dose was expressed as percentage of administered dose. |
| Time Frame | Days 1-2: 0-24 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 14 | 5 |
| Regorafenib metabolites M-7 |
3.607
(1.124)
|
1.309
(0.649)
|
| Regorafenib metabolites M-8 |
1.120
(0.737)
|
0.184
(0.229)
|
| Title | AUC (Area Under the Plasma Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation. AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. |
| Time Frame | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib (n=6, 3) |
59.5
(26.1)
|
98.7
(71.0)
|
| Regorafenib metabolites M-2 (n=13, 4) |
32.6
(89.0)
|
20.8
(65.4)
|
| Regorafenib metabolites M-5 (n=0, 0) |
NA
(NA)
|
NA
(NA)
|
| Title | AUC(0-24) (AUC From Time Zero to 24 Hours p.a. After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation. The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; AUC(0-24) is defined as AUC divided from zero to 24 hours after single (first) dose. |
| Time Frame | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| In Normal/mild renal impairment group, participants analyzed for regorafenib, M-2 and M-5 are n=18, 18, and 17 respectively. In Severe renal impairment group, participants analyzed for regorafenib, M-2 and M-5 are n=6, 6, and 5 respectively. Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib |
30.0
(39.8)
|
28.4
(62.0)
|
| Regorafenib metabolites M-2 |
13.5
(70.0)
|
7.93
(72.7)
|
| Regorafenib metabolites M-5 |
1.17
(116)
|
0.474
(101)
|
| Title | Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation.Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. |
| Time Frame | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib |
2.45
(47)
|
2.00
(69.7)
|
| Regorafenib metabolites M-2 |
1.01
(66.7)
|
0.525
(69.6)
|
| Regorafenib metabolites M-5 |
0.0877
(125)
|
0.0341
(67.0)
|
| Title | Tmax (Time to Reach Maximum Drug Concentration in Plasma After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation.Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content. |
| Time Frame | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib |
4.03
|
3.04
|
| Regorafenib metabolites M-2 |
4.03
|
6.04
|
| Regorafenib metabolites M-5 |
47.8
|
48.9
|
| Title | Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | based on non-compartmental PK evaluation. |
| Time Frame | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib |
95.7
|
95.8
|
| Regorafenib metabolites M-2 |
95.7
|
95.8
|
| Regorafenib metabolites M-5 |
95.7
|
95.8
|
| Title | t1/2 (Half-life Associated With the Terminal Slope) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation. t1/2 refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in hours (h) and derived from the terminal slope of the concentration versus time curve. |
| Time Frame | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib (n=6, 3) |
28.7
(23.0)
|
27.9
(32.0)
|
| Regorafenib metabolites M-2 (n=13, 4) |
26.2
(25.7)
|
25.5
(24.0)
|
| Regorafenib metabolites M-5 (n=0, 0) |
NA
(NA)
|
NA
(NA)
|
| Title | CL/F (Total Body Clearance of Drug After Extravascular Administration) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation.Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Time Frame | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib (n=6, 3) |
2.69
(26.1)
|
1.62
(71.0)
|
| Regorafenib metabolites M-2 (n=13, 4) |
5.08
(89.0)
|
7.95
(65.4)
|
| Regorafenib metabolites M-5 (n=0, 0) |
NA
(NA)
|
NA
(NA)
|
| Title | Vz/F (Apparent Volume of Distribution During Terminal Phase After Single (First) Oral Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation.Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Time Frame | Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib (n=6, 3) |
111
(31.9)
|
65.2
(81.0)
|
| Regorafenib metabolites M-2 (n=13, 4) |
192
(83.8)
|
292
(71.1)
|
| Regorafenib metabolites M-5 (n=0, 0) |
NA
(NA)
|
NA
(NA)
|
| Title | AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation. |
| Time Frame | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| In Normal/mild renal impairment group, number of participants analyzed is 13. In Severe renal impairment group, number of participants analyzed is 4. Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib |
56.0
(56.4)
|
45.2
(45.8)
|
| Regorafenib metabolites M-2 |
53.9
(63.1)
|
35.0
(207)
|
| Regorafenib metabolites M-5 |
49.7
(130)
|
34.2
(438)
|
| Title | Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation.Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. |
| Time Frame | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 13 | 4 |
| Regorafenib |
3.52
(54.9)
|
2.87
(62.2)
|
| Regorafenib metabolites M-2 |
3.52
(58.8)
|
2.29
(257)
|
| Regorafenib metabolites M-5 |
3.25
(133)
|
2.23
(659)
|
| Title | AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | based on non-compartmental PK evaluation. |
| Time Frame | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 13 | 4 |
| Regorafenib |
133
(55.1)
|
111
(54.8)
|
| Regorafenib metabolites M-2 |
136
(64.9)
|
92.3
(280)
|
| Regorafenib metabolites M-5 |
183
(128)
|
134
(459)
|
| Title | Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | based on non-compartmental PK evaluation |
| Time Frame | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 13 | 4 |
| Regorafenib |
3.97
|
4.25
|
| Regorafenib metabolites M-2 |
4.12
|
4.00
|
| Regorafenib metabolites M-5 |
0.000
|
0.000
|
| Title | Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | based on non-compartmental PK evaluation |
| Time Frame | Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 13 | 4 |
| Regorafenib |
96.0
|
95.3
|
| Regorafenib metabolites M-2 |
96.0
|
95.3
|
| Regorafenib metabolites M-5 |
96.0
|
95.3
|
| Title | RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation. Accumulation ratio based on maximum plasma concentration (Cmax) was calculated as ratio of Cmax,md and Cmax. |
| Time Frame | Up to 25 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 13 | 4 |
| Regorafenib |
1.51
(60.0)
|
1.96
(68.2)
|
| Regorafenib metabolites M-2 |
3.83
(44.9)
|
5.94
(216)
|
| Regorafenib metabolites M-5 |
39.7
(94.0)
|
81.8
(515)
|
| Title | RAAUC (Accumulation Ratio Calculated From AUC(0-24)md and AUC(0-24)) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation. RAAUC calculated as ratio of AUC(0-24)md and AUC(0-24). |
| Time Frame | Up to 25 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| In Normal/mild renal impairment group, participants analyzed for regorafenib, M-2 and M-5 are n=13, 13 and 12 respectively. In Severe renal impairment group, participants analyzed for regorafenib, M-2 and M-5 are n=4, 4 and 3 respectively. Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 18 | 6 |
| Regorafenib |
1.97
(57.1)
|
1.96
(52.0)
|
| Regorafenib metabolites M-2 |
4.32
(45.0)
|
6.00
(172)
|
| Regorafenib metabolites M-5 |
48.3
(76.0)
|
87.0
(585)
|
| Title | RLin (Linearity Factor Calculated as Ratio From AUC(0-24)md and AUC) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5 |
|---|---|
| Description | Based on non-compartmental PK evaluation. RLin is the linearity factor of PK after multiple administrations of identical doses calculated as ratio of AUC(0-24)md and AUC. |
| Time Frame | Up to 25 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 9 | 2 |
| Regorafenib (n=5, 2) |
0.957
(49.2)
|
0.469
(5.24)
|
| Regorafenib metabolites M-2 (n= 9, 2) |
1.98
(40.7)
|
1.19
(144)
|
| Regorafenib metabolites M-5 (n=0, 0) |
NA
(NA)
|
NA
(NA)
|
| Title | AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8 |
|---|---|
| Description | based on non-compartmental PK evaluation |
| Time Frame | Days 21-22: 0-24 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 12 | 4 |
| Regorafenib metabolites M-7 |
5.094
(2.322)
|
1.647
(0.753)
|
| Regorafenib metabolites M-8 |
2.566
(1.561)
|
1.238
(0.684)
|
| Title | AE,ur(0-10) Stage 1 (Amount of Drug Excreted Via Urine During the Collection Interval 0-10 Hours Post Administration) for Metabolites M-7 and M-8 |
|---|---|
| Description | based on non-compartmental PK evaluation |
| Time Frame | Days 1-2: 0-10 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 14 | 5 |
| Regorafenib metabolites M-7 |
1.752
(0.611)
|
0.449
(0.301)
|
| Regorafenib metabolites M-8 |
0.486
(0.382)
|
0.053
(0.089)
|
| Title | AE,ur(10-24) Stage 1 ((Amount of Drug Excreted Via Urine During the Collection Interval 10-24 Hours Post Administration) for Metabolites M-7 and M-8 |
|---|---|
| Description | based on non-compartmental PK evaluation |
| Time Frame | Days 1-2: 10-24 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 14 | 6 |
| Regorafenib metabolites M-7 |
1.855
(0.629)
|
0.746
(0.441)
|
| Regorafenib metabolites M-8 |
0.634
(0.374)
|
0.117
(0.133)
|
| Title | AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8 |
|---|---|
| Description | based on non-compartmental PK evaluation |
| Time Frame | Days 21-22: 0-10 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 12 | 4 |
| Regorafenib metabolites M-7 |
2.655
(1.346)
|
0.600
(0.255)
|
| Regorafenib metabolites M-8 |
1.292
(0.902)
|
0.469
(0.338)
|
| Title | AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8 |
|---|---|
| Description | based on non-compartmental PK evaluation |
| Time Frame | Days 21-22: 10-24 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid pharmacokinetic profile for non compartmental analysis were reported. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 12 | 4 |
| Regorafenib metabolites M-7 |
2.440
(1.098)
|
1.047
(0.738)
|
| Regorafenib metabolites M-8 |
1.274
(0.712)
|
0.769
(0.497)
|
| Title | Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors) |
|---|---|
| Description | Positron emission tomography - computed tomography (ET-CT), CT, or magnetic resonance imaging (MRI) scans of all anatomic regions involved with the disease were performed to assess tumor response using the Response Evaluation Criteria in Solid Tumors, Version 1.1. (RECIST v1.1). Bone metastases were assessed by bone scintigraphy (bone scan). Tumor measurements and evaluation of tumor response were performed at baseline and within the last 7 days of Cycle 2. Thereafter, if subjects continued regorafenib treatment, tumor assessments were performed after every third cycle and at the end-of-treatment (EOT) visit. In addition, outcome of "Assessment of Bone Metastases by Scintigraphy if Applicable (Bone Scan)" was registered, the results of which has been reported as tumor response in this outcome as well. |
| Time Frame | Up to 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Normal/mild renal impairment group had only tumor assessments at screening, thus excluded from efficacy analysis. |
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment |
|---|---|---|
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. |
| Measure Participants | 15 | 6 |
| Complete response (CR) |
0
0%
|
0
0%
|
| Partial response (PR) |
0
0%
|
0
0%
|
| Stable disease (SD) |
10
55.6%
|
5
83.3%
|
| Non CR/Non PD |
0
0%
|
0
0%
|
| Progressive disease (PD) |
5
27.8%
|
1
16.7%
|
| Not evaluable |
0
0%
|
0
0%
|
Adverse Events
| Time Frame | From start of study treatment until 30 days after last dose of study medication. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety was assessed routinely and on an ongoing basis | |||
| Arm/Group Title | Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | ||
| Arm/Group Description | Participants with normal/mild renal impairment received Regorafenib 160 mg o.d.as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | Participants with severe renal impairment received Regorafenib 160 mg o.d. as a single dose in Stage 1, Day 1 with a washout of at least 5 days, followed by multiple dosing in an intermittent administration schedule (3 week on / 1 week off) over 2 cycles in Stage 2 (56 days). Cycle 2 started immediately after Cycle 1. A Cycle for this study is defined as 28 days. | ||
All Cause Mortality |
||||
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/18 (50%) | 2/6 (33.3%) | ||
| Cardiac disorders | ||||
| Stress cardiomyopathy | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Intestinal obstruction | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Pancreatitis | 1/18 (5.6%) | 3 | 0/6 (0%) | 0 |
| Small intestinal obstruction | 2/18 (11.1%) | 4 | 0/6 (0%) | 0 |
| General disorders | ||||
| Chest pain | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Muscular weakness | 1/18 (5.6%) | 1 | 1/6 (16.7%) | 1 |
| Renal and urinary disorders | ||||
| Haematuria | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Pleural effusion | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Vascular disorders | ||||
| Deep vein thrombosis | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Embolism | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment | Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/18 (100%) | 6/6 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/18 (11.1%) | 6 | 2/6 (33.3%) | 5 |
| Neutropenia | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Thrombocytopenia | 1/18 (5.6%) | 1 | 2/6 (33.3%) | 3 |
| Cardiac disorders | ||||
| Angina pectoris | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Tachycardia | 2/18 (11.1%) | 2 | 0/6 (0%) | 0 |
| Ear and labyrinth disorders | ||||
| Ear discomfort | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Eye disorders | ||||
| Cataract | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Chalazion | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Eye pain | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Glaucoma | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Vision blurred | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Abdominal distension | 1/18 (5.6%) | 1 | 1/6 (16.7%) | 1 |
| Abdominal pain | 5/18 (27.8%) | 12 | 3/6 (50%) | 6 |
| Abdominal pain lower | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Abdominal pain upper | 1/18 (5.6%) | 1 | 1/6 (16.7%) | 1 |
| Cheilitis | 1/18 (5.6%) | 1 | 3/6 (50%) | 3 |
| Constipation | 5/18 (27.8%) | 7 | 3/6 (50%) | 4 |
| Diarrhoea | 8/18 (44.4%) | 16 | 4/6 (66.7%) | 12 |
| Diverticulum | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Dry mouth | 2/18 (11.1%) | 2 | 2/6 (33.3%) | 3 |
| Dyspepsia | 4/18 (22.2%) | 6 | 1/6 (16.7%) | 1 |
| Eructation | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Faecal incontinence | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Faecaloma | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Flatulence | 2/18 (11.1%) | 3 | 0/6 (0%) | 0 |
| Gastrointestinal pain | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Gastrooesophageal reflux disease | 3/18 (16.7%) | 4 | 1/6 (16.7%) | 1 |
| Glossodynia | 1/18 (5.6%) | 1 | 1/6 (16.7%) | 2 |
| Haematemesis | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Inguinal hernia | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Lip ulceration | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Nausea | 10/18 (55.6%) | 20 | 6/6 (100%) | 8 |
| Odynophagia | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Proctalgia | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Retching | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Stomatitis | 3/18 (16.7%) | 6 | 2/6 (33.3%) | 8 |
| Toothache | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Vomiting | 6/18 (33.3%) | 8 | 4/6 (66.7%) | 9 |
| General disorders | ||||
| Asthenia | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Chest pain | 3/18 (16.7%) | 3 | 0/6 (0%) | 0 |
| Chills | 2/18 (11.1%) | 2 | 2/6 (33.3%) | 2 |
| Drug intolerance | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Early satiety | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Fatigue | 13/18 (72.2%) | 24 | 3/6 (50%) | 7 |
| Impaired healing | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Medical device site reaction | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Mucosal inflammation | 4/18 (22.2%) | 14 | 1/6 (16.7%) | 1 |
| Oedema | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Oedema peripheral | 2/18 (11.1%) | 2 | 0/6 (0%) | 0 |
| Pyrexia | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Vessel puncture site bruise | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Infections and infestations | ||||
| Candida infection | 3/18 (16.7%) | 4 | 0/6 (0%) | 0 |
| Cellulitis | 2/18 (11.1%) | 2 | 0/6 (0%) | 0 |
| Eye infection | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Pneumonia | 2/18 (11.1%) | 2 | 0/6 (0%) | 0 |
| Sinusitis | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Subcutaneous abscess | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Urinary tract infection | 1/18 (5.6%) | 1 | 1/6 (16.7%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Ankle fracture | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Arthropod bite | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Contusion | 2/18 (11.1%) | 2 | 1/6 (16.7%) | 1 |
| Face injury | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Fall | 1/18 (5.6%) | 1 | 1/6 (16.7%) | 1 |
| Procedural site reaction | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Subcutaneous haematoma | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 2/18 (11.1%) | 2 | 1/6 (16.7%) | 2 |
| Amylase increased | 0/18 (0%) | 0 | 1/6 (16.7%) | 8 |
| Aspartate aminotransferase increased | 1/18 (5.6%) | 3 | 1/6 (16.7%) | 2 |
| Blood bilirubin increased | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Blood creatinine increased | 2/18 (11.1%) | 3 | 2/6 (33.3%) | 4 |
| Blood fibrinogen decreased | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Blood urea increased | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Cardiac murmur | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Haemoglobin decreased | 0/18 (0%) | 0 | 2/6 (33.3%) | 2 |
| International normalised ratio increased | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Lipase increased | 0/18 (0%) | 0 | 1/6 (16.7%) | 10 |
| Troponin increased | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Weight decreased | 6/18 (33.3%) | 9 | 1/6 (16.7%) | 3 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 11/18 (61.1%) | 23 | 3/6 (50%) | 5 |
| Dehydration | 3/18 (16.7%) | 4 | 0/6 (0%) | 0 |
| Hyperglycaemia | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Hyperlipasaemia | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Hyperuricaemia | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Hypocalcaemia | 0/18 (0%) | 0 | 1/6 (16.7%) | 3 |
| Hypoglycaemia | 0/18 (0%) | 0 | 1/6 (16.7%) | 2 |
| Hypokalaemia | 1/18 (5.6%) | 3 | 0/6 (0%) | 0 |
| Hypomagnesaemia | 2/18 (11.1%) | 2 | 1/6 (16.7%) | 4 |
| Hyponatraemia | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Hypophosphataemia | 1/18 (5.6%) | 3 | 1/6 (16.7%) | 1 |
| Lactose intolerance | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 5/18 (27.8%) | 15 | 3/6 (50%) | 4 |
| Back pain | 4/18 (22.2%) | 6 | 2/6 (33.3%) | 3 |
| Muscle spasms | 6/18 (33.3%) | 14 | 0/6 (0%) | 0 |
| Muscular weakness | 2/18 (11.1%) | 6 | 0/6 (0%) | 0 |
| Musculoskeletal chest pain | 2/18 (11.1%) | 3 | 0/6 (0%) | 0 |
| Musculoskeletal discomfort | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Musculoskeletal pain | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Musculoskeletal stiffness | 2/18 (11.1%) | 2 | 0/6 (0%) | 0 |
| Myalgia | 6/18 (33.3%) | 15 | 2/6 (33.3%) | 3 |
| Neck mass | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Neck pain | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Pain in extremity | 1/18 (5.6%) | 5 | 0/6 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer pain | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Nervous system disorders | ||||
| Disturbance in attention | 2/18 (11.1%) | 2 | 0/6 (0%) | 0 |
| Dizziness | 4/18 (22.2%) | 4 | 2/6 (33.3%) | 2 |
| Dysgeusia | 3/18 (16.7%) | 4 | 0/6 (0%) | 0 |
| Headache | 10/18 (55.6%) | 18 | 2/6 (33.3%) | 5 |
| Neuropathy peripheral | 2/18 (11.1%) | 7 | 0/6 (0%) | 0 |
| Paraesthesia | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Peripheral sensory neuropathy | 2/18 (11.1%) | 2 | 0/6 (0%) | 0 |
| Sensory disturbance | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Psychiatric disorders | ||||
| Agitation | 1/18 (5.6%) | 3 | 0/6 (0%) | 0 |
| Anxiety | 1/18 (5.6%) | 3 | 0/6 (0%) | 0 |
| Insomnia | 3/18 (16.7%) | 3 | 1/6 (16.7%) | 1 |
| Renal and urinary disorders | ||||
| Dysuria | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Proteinuria | 1/18 (5.6%) | 1 | 3/6 (50%) | 6 |
| Urinary retention | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Dysmenorrhoea | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Menstruation irregular | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Pelvic pain | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 4/18 (22.2%) | 5 | 1/6 (16.7%) | 1 |
| Dysphonia | 8/18 (44.4%) | 12 | 2/6 (33.3%) | 9 |
| Dyspnoea | 6/18 (33.3%) | 8 | 1/6 (16.7%) | 1 |
| Dyspnoea exertional | 1/18 (5.6%) | 1 | 2/6 (33.3%) | 2 |
| Epistaxis | 2/18 (11.1%) | 2 | 1/6 (16.7%) | 1 |
| Haemoptysis | 3/18 (16.7%) | 3 | 0/6 (0%) | 0 |
| Hiccups | 0/18 (0%) | 0 | 2/6 (33.3%) | 2 |
| Nasal congestion | 1/18 (5.6%) | 7 | 0/6 (0%) | 0 |
| Oropharyngeal pain | 2/18 (11.1%) | 2 | 1/6 (16.7%) | 1 |
| Productive cough | 1/18 (5.6%) | 3 | 0/6 (0%) | 0 |
| Rhinorrhoea | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 4/18 (22.2%) | 7 | 0/6 (0%) | 0 |
| Decubitus ulcer | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Dry skin | 2/18 (11.1%) | 2 | 1/6 (16.7%) | 1 |
| Eczema | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Erythema | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Hyperhidrosis | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Nail disorder | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Night sweats | 1/18 (5.6%) | 1 | 1/6 (16.7%) | 1 |
| Pain of skin | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Palmar erythema | 1/18 (5.6%) | 2 | 0/6 (0%) | 0 |
| Palmar-plantar erythrodysaesthesia syndrome | 10/18 (55.6%) | 32 | 3/6 (50%) | 15 |
| Pruritus | 2/18 (11.1%) | 3 | 1/6 (16.7%) | 1 |
| Rash | 5/18 (27.8%) | 12 | 2/6 (33.3%) | 3 |
| Rash maculo-papular | 1/18 (5.6%) | 1 | 1/6 (16.7%) | 2 |
| Skin hyperpigmentation | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Skin lesion | 0/18 (0%) | 0 | 1/6 (16.7%) | 1 |
| Swelling face | 1/18 (5.6%) | 1 | 0/6 (0%) | 0 |
| Vascular disorders | ||||
| Flushing | 1/18 (5.6%) | 1 | 1/6 (16.7%) | 1 |
| Hot flush | 2/18 (11.1%) | 2 | 0/6 (0%) | 0 |
| Hypertension | 8/18 (44.4%) | 10 | 4/6 (66.7%) | 10 |
| Hypotension | 2/18 (11.1%) | 2 | 1/6 (16.7%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | Bayer AG |
| Phone | |
| clinical-trials-contact@bayer.com |
Responsible Party:
Bayer
ClinicalTrials.gov Identifier:
NCT01853046
Other Study ID Numbers:
- 16653
First Posted:
May 14, 2013
Last Update Posted:
Feb 20, 2017
Last Verified:
Dec 1, 2016