Trial Outcomes & Findings for Pharmacokinetics and Safety of Regorafenib (BAY73-4506) in Cancer Subjects With Severe Renal Impairment (NCT NCT01853046)
NCT ID: NCT01853046
Last Updated: 2017-02-20
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Results posted on
2017-02-20
Participant Flow
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.
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
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
6
|
|
Overall Study
Received Treatment
|
18
|
6
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
18
|
6
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Adverse Event
|
4
|
2
|
|
Overall Study
Disease progression
|
13
|
3
|
Baseline Characteristics
Pharmacokinetics and Safety of Regorafenib (BAY73-4506) in Cancer Subjects With Severe Renal Impairment
Baseline characteristics by cohort
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.0 years
STANDARD_DEVIATION 9.6 • n=99 Participants
|
64.2 years
STANDARD_DEVIATION 6.9 • n=107 Participants
|
62.5 years
STANDARD_DEVIATION 8.9 • n=206 Participants
|
|
Gender
Female
|
9 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Gender
Male
|
9 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-doseBased 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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
AUC(0-tlast) [Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point >LLOQ (Lower Limit of Quantification)] for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
67.2 mg*h/L
Geometric Coefficient of Variation 45.5
|
76.6 mg*h/L
Geometric Coefficient of Variation 50.3
|
|
AUC(0-tlast) [Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point >LLOQ (Lower Limit of Quantification)] for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
27.8 mg*h/L
Geometric Coefficient of Variation 80.4
|
19.0 mg*h/L
Geometric Coefficient of Variation 58.7
|
|
AUC(0-tlast) [Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point >LLOQ (Lower Limit of Quantification)] for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
5.25 mg*h/L
Geometric Coefficient of Variation 145
|
2.34 mg*h/L
Geometric Coefficient of Variation 79.8
|
PRIMARY outcome
Timeframe: Days 1-2: 0-24 hoursPopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Amount of drug excreted into urine during the collection interval 0-24 hours post dose was expressed as percentage of administered dose.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=14 Participants
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
n=5 Participants
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.
|
|---|---|---|
|
AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0-24 Hours Post Administration) for Metabolites M-7 and M-8
Regorafenib metabolites M-7
|
3.607 percentage of dose
Standard Deviation 1.124
|
1.309 percentage of dose
Standard Deviation 0.649
|
|
AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0-24 Hours Post Administration) for Metabolites M-7 and M-8
Regorafenib metabolites M-8
|
1.120 percentage of dose
Standard Deviation 0.737
|
0.184 percentage of dose
Standard Deviation 0.229
|
SECONDARY outcome
Timeframe: Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dosePopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
AUC (Area Under the Plasma Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib (n=6, 3)
|
59.5 mg*h/L
Geometric Coefficient of Variation 26.1
|
98.7 mg*h/L
Geometric Coefficient of Variation 71.0
|
|
AUC (Area Under the Plasma Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2 (n=13, 4)
|
32.6 mg*h/L
Geometric Coefficient of Variation 89.0
|
20.8 mg*h/L
Geometric Coefficient of Variation 65.4
|
|
AUC (Area Under the Plasma Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5 (n=0, 0)
|
NA mg*h/L
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
NA mg*h/L
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
SECONDARY outcome
Timeframe: Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
AUC(0-24) (AUC From Time Zero to 24 Hours p.a. After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
1.17 mg*h/L
Geometric Coefficient of Variation 116
|
0.474 mg*h/L
Geometric Coefficient of Variation 101
|
|
AUC(0-24) (AUC From Time Zero to 24 Hours p.a. After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
30.0 mg*h/L
Geometric Coefficient of Variation 39.8
|
28.4 mg*h/L
Geometric Coefficient of Variation 62.0
|
|
AUC(0-24) (AUC From Time Zero to 24 Hours p.a. After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
13.5 mg*h/L
Geometric Coefficient of Variation 70.0
|
7.93 mg*h/L
Geometric Coefficient of Variation 72.7
|
SECONDARY outcome
Timeframe: Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-doseBased 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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
2.45 mg/L
Geometric Coefficient of Variation 47
|
2.00 mg/L
Geometric Coefficient of Variation 69.7
|
|
Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
1.01 mg/L
Geometric Coefficient of Variation 66.7
|
0.525 mg/L
Geometric Coefficient of Variation 69.6
|
|
Cmax (Maximum Drug Concentration in Plasma After Single (First) Dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
0.0877 mg/L
Geometric Coefficient of Variation 125
|
0.0341 mg/L
Geometric Coefficient of Variation 67.0
|
SECONDARY outcome
Timeframe: Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-doseBased 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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
Tmax (Time to Reach Maximum Drug Concentration in Plasma After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
4.03 h
Interval 1.0 to 24.0
|
3.04 h
Interval 1.0 to 23.75
|
|
Tmax (Time to Reach Maximum Drug Concentration in Plasma After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
4.03 h
Interval 1.0 to 24.0
|
6.04 h
Interval 1.98 to 23.8
|
|
Tmax (Time to Reach Maximum Drug Concentration in Plasma After Single (First) Dose) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
47.8 h
Interval 6.0 to 96.1
|
48.9 h
Interval 24.1 to 95.8
|
SECONDARY outcome
Timeframe: Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dosebased on non-compartmental PK evaluation.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
95.7 h
Interval 46.4 to 96.3
|
95.8 h
Interval 95.6 to 96.0
|
|
Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
95.7 h
Interval 46.4 to 96.3
|
95.8 h
Interval 95.6 to 96.0
|
|
Tlast (Time of Last Data Point >LLOQ) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
95.7 h
Interval 46.4 to 96.3
|
95.8 h
Interval 95.6 to 96.0
|
SECONDARY outcome
Timeframe: Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dosePopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
t1/2 (Half-life Associated With the Terminal Slope) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib (n=6, 3)
|
28.7 h
Geometric Coefficient of Variation 23.0
|
27.9 h
Geometric Coefficient of Variation 32.0
|
|
t1/2 (Half-life Associated With the Terminal Slope) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2 (n=13, 4)
|
26.2 h
Geometric Coefficient of Variation 25.7
|
25.5 h
Geometric Coefficient of Variation 24.0
|
|
t1/2 (Half-life Associated With the Terminal Slope) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5 (n=0, 0)
|
NA h
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
NA h
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
SECONDARY outcome
Timeframe: Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dosePopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
CL/F (Total Body Clearance of Drug After Extravascular Administration) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib (n=6, 3)
|
2.69 L/H
Geometric Coefficient of Variation 26.1
|
1.62 L/H
Geometric Coefficient of Variation 71.0
|
|
CL/F (Total Body Clearance of Drug After Extravascular Administration) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2 (n=13, 4)
|
5.08 L/H
Geometric Coefficient of Variation 89.0
|
7.95 L/H
Geometric Coefficient of Variation 65.4
|
|
CL/F (Total Body Clearance of Drug After Extravascular Administration) After Single (First) Dose for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5 (n=0, 0)
|
NA L/H
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
NA L/H
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
SECONDARY outcome
Timeframe: Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dosePopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
Vz/F (Apparent Volume of Distribution During Terminal Phase After Single (First) Oral Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib (n=6, 3)
|
111 L
Geometric Coefficient of Variation 31.9
|
65.2 L
Geometric Coefficient of Variation 81.0
|
|
Vz/F (Apparent Volume of Distribution During Terminal Phase After Single (First) Oral Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2 (n=13, 4)
|
192 L
Geometric Coefficient of Variation 83.8
|
292 L
Geometric Coefficient of Variation 71.1
|
|
Vz/F (Apparent Volume of Distribution During Terminal Phase After Single (First) Oral Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5 (n=0, 0)
|
NA L
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
NA L
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
SECONDARY outcome
Timeframe: Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10 and 24 hours post-dosePopulation: 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.
Based on non-compartmental PK evaluation.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
56.0 mg*h/L
Geometric Coefficient of Variation 56.4
|
45.2 mg*h/L
Geometric Coefficient of Variation 45.8
|
|
AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
53.9 mg*h/L
Geometric Coefficient of Variation 63.1
|
35.0 mg*h/L
Geometric Coefficient of Variation 207
|
|
AUC(0-24)md ((AUC(0-24) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
49.7 mg*h/L
Geometric Coefficient of Variation 130
|
34.2 mg*h/L
Geometric Coefficient of Variation 438
|
SECONDARY outcome
Timeframe: Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dosePopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=13 Participants
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
n=4 Participants
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.
|
|---|---|---|
|
Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
3.52 mg/L
Geometric Coefficient of Variation 54.9
|
2.87 mg/L
Geometric Coefficient of Variation 62.2
|
|
Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
3.52 mg/L
Geometric Coefficient of Variation 58.8
|
2.29 mg/L
Geometric Coefficient of Variation 257
|
|
Cmax,md (Cmax After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
3.25 mg/L
Geometric Coefficient of Variation 133
|
2.23 mg/L
Geometric Coefficient of Variation 659
|
SECONDARY outcome
Timeframe: Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dosePopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
based on non-compartmental PK evaluation.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=13 Participants
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
n=4 Participants
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.
|
|---|---|---|
|
AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
133 mg*h/L
Geometric Coefficient of Variation 55.1
|
111 mg*h/L
Geometric Coefficient of Variation 54.8
|
|
AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
136 mg*h/L
Geometric Coefficient of Variation 64.9
|
92.3 mg*h/L
Geometric Coefficient of Variation 280
|
|
AUC(0-tlast)md (AUC(0-tlast) After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
183 mg*h/L
Geometric Coefficient of Variation 128
|
134 mg*h/L
Geometric Coefficient of Variation 459
|
SECONDARY outcome
Timeframe: Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dosePopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
based on non-compartmental PK evaluation
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=13 Participants
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
n=4 Participants
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.
|
|---|---|---|
|
Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
3.97 h
Interval 0.0 to 23.8
|
4.25 h
Interval 0.0 to 10.0
|
|
Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
4.12 h
Interval 0.0 to 23.9
|
4.00 h
Interval 0.0 to 10.0
|
|
Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
0.000 h
Interval 0.0 to 24.0
|
0.000 h
Interval 0.0 to 8.0
|
SECONDARY outcome
Timeframe: Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dosePopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
based on non-compartmental PK evaluation
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=13 Participants
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
n=4 Participants
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.
|
|---|---|---|
|
Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
96.0 h
Interval 48.1 to 96.5
|
95.3 h
Interval 94.3 to 96.0
|
|
Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
96.0 h
Interval 48.1 to 96.5
|
95.3 h
Interval 94.3 to 96.0
|
|
Tlast,md (Tlast After Multiple-dose Administration) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
96.0 h
Interval 48.1 to 96.5
|
95.3 h
Interval 94.3 to 96.0
|
SECONDARY outcome
Timeframe: Up to 25 daysPopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
Based on non-compartmental PK evaluation. Accumulation ratio based on maximum plasma concentration (Cmax) was calculated as ratio of Cmax,md and Cmax.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=13 Participants
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
n=4 Participants
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.
|
|---|---|---|
|
RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
1.51 Accumulation Ratio
Geometric Coefficient of Variation 60.0
|
1.96 Accumulation Ratio
Geometric Coefficient of Variation 68.2
|
|
RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
3.83 Accumulation Ratio
Geometric Coefficient of Variation 44.9
|
5.94 Accumulation Ratio
Geometric Coefficient of Variation 216
|
|
RACmax (Accumulation Ratio Calculated From Cmax,md and Cmax) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
39.7 Accumulation Ratio
Geometric Coefficient of Variation 94.0
|
81.8 Accumulation Ratio
Geometric Coefficient of Variation 515
|
SECONDARY outcome
Timeframe: Up to 25 daysPopulation: 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.
Based on non-compartmental PK evaluation. RAAUC calculated as ratio of AUC(0-24)md and AUC(0-24).
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=18 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
RAAUC (Accumulation Ratio Calculated From AUC(0-24)md and AUC(0-24)) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib
|
1.97 Accumulation Ratio
Geometric Coefficient of Variation 57.1
|
1.96 Accumulation Ratio
Geometric Coefficient of Variation 52.0
|
|
RAAUC (Accumulation Ratio Calculated From AUC(0-24)md and AUC(0-24)) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-2
|
4.32 Accumulation Ratio
Geometric Coefficient of Variation 45.0
|
6.00 Accumulation Ratio
Geometric Coefficient of Variation 172
|
|
RAAUC (Accumulation Ratio Calculated From AUC(0-24)md and AUC(0-24)) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5
|
48.3 Accumulation Ratio
Geometric Coefficient of Variation 76.0
|
87.0 Accumulation Ratio
Geometric Coefficient of Variation 585
|
SECONDARY outcome
Timeframe: Up to 25 daysPopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=9 Participants
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
n=2 Participants
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.
|
|---|---|---|
|
RLin (Linearity Factor Calculated as Ratio From AUC(0-24)md and AUC) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib (n=5, 2)
|
0.957 Linearity factor calculated as ratio
Geometric Coefficient of Variation 49.2
|
0.469 Linearity factor calculated as ratio
Geometric Coefficient of Variation 5.24
|
|
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
Regorafenib metabolites M-2 (n= 9, 2)
|
1.98 Linearity factor calculated as ratio
Geometric Coefficient of Variation 40.7
|
1.19 Linearity factor calculated as ratio
Geometric Coefficient of Variation 144
|
|
RLin (Linearity Factor Calculated as Ratio From AUC(0-24)md and AUC) for Regorafenib and Its Pharmacologically Active Metabolites M-2 and M-5
Regorafenib metabolites M-5 (n=0, 0)
|
NA Linearity factor calculated as ratio
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
NA Linearity factor calculated as ratio
Geometric Coefficient of Variation NA
Number of analyzed subjects is zero.
|
SECONDARY outcome
Timeframe: Days 21-22: 0-24 hoursPopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
based on non-compartmental PK evaluation
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=12 Participants
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
n=4 Participants
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.
|
|---|---|---|
|
AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8
Regorafenib metabolites M-7
|
5.094 percentage of dose
Standard Deviation 2.322
|
1.647 percentage of dose
Standard Deviation 0.753
|
|
AE,ur(0-24)md (AE,ur(0-24) After Multiple-dose Administration) for Metabolites M-7 and M-8
Regorafenib metabolites M-8
|
2.566 percentage of dose
Standard Deviation 1.561
|
1.238 percentage of dose
Standard Deviation 0.684
|
SECONDARY outcome
Timeframe: Days 1-2: 0-10 hoursPopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
based on non-compartmental PK evaluation
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=14 Participants
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
n=5 Participants
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.
|
|---|---|---|
|
AE,ur(0-10) Stage 1 (Amount of Drug Excreted Via Urine During the Collection Interval 0-10 Hours Post Administration) for Metabolites M-7 and M-8
Regorafenib metabolites M-7
|
1.752 percentage of dose
Standard Deviation 0.611
|
0.449 percentage of dose
Standard Deviation 0.301
|
|
AE,ur(0-10) Stage 1 (Amount of Drug Excreted Via Urine During the Collection Interval 0-10 Hours Post Administration) for Metabolites M-7 and M-8
Regorafenib metabolites M-8
|
0.486 percentage of dose
Standard Deviation 0.382
|
0.053 percentage of dose
Standard Deviation 0.089
|
SECONDARY outcome
Timeframe: Days 1-2: 10-24 hoursPopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
based on non-compartmental PK evaluation
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=14 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
AE,ur(10-24) Stage 1 ((Amount of Drug Excreted Via Urine During the Collection Interval 10-24 Hours Post Administration) for Metabolites M-7 and M-8
Regorafenib metabolites M-7
|
1.855 percentage of dose
Standard Deviation 0.629
|
0.746 percentage of dose
Standard Deviation 0.441
|
|
AE,ur(10-24) Stage 1 ((Amount of Drug Excreted Via Urine During the Collection Interval 10-24 Hours Post Administration) for Metabolites M-7 and M-8
Regorafenib metabolites M-8
|
0.634 percentage of dose
Standard Deviation 0.374
|
0.117 percentage of dose
Standard Deviation 0.133
|
SECONDARY outcome
Timeframe: Days 21-22: 0-10 hoursPopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
based on non-compartmental PK evaluation
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=12 Participants
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
n=4 Participants
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.
|
|---|---|---|
|
AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8
Regorafenib metabolites M-7
|
2.655 percentage of dose
Standard Deviation 1.346
|
0.600 percentage of dose
Standard Deviation 0.255
|
|
AE,ur(0-10) Stage 2 for Metabolites M-7 and M-8
Regorafenib metabolites M-8
|
1.292 percentage of dose
Standard Deviation 0.902
|
0.469 percentage of dose
Standard Deviation 0.338
|
SECONDARY outcome
Timeframe: Days 21-22: 10-24 hoursPopulation: Participants with a valid pharmacokinetic profile for non compartmental analysis were reported.
based on non-compartmental PK evaluation
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=12 Participants
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
n=4 Participants
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.
|
|---|---|---|
|
AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8
Regorafenib metabolites M-8
|
1.274 percentage of dose
Standard Deviation 0.712
|
0.769 percentage of dose
Standard Deviation 0.497
|
|
AE,ur(10-24) Stage 2 for Metabolites M-7 and M-8
Regorafenib metabolites M-7
|
2.440 percentage of dose
Standard Deviation 1.098
|
1.047 percentage of dose
Standard Deviation 0.738
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 6 monthsPopulation: Participants in the Normal/mild renal impairment group had only tumor assessments at screening, thus excluded from efficacy analysis.
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.
Outcome measures
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Renal Impairment
n=15 Participants
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
n=6 Participants
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.
|
|---|---|---|
|
Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors)
Complete response (CR)
|
0 participants
|
0 participants
|
|
Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors)
Partial response (PR)
|
0 participants
|
0 participants
|
|
Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors)
Stable disease (SD)
|
10 participants
|
5 participants
|
|
Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors)
Non CR/Non PD
|
0 participants
|
0 participants
|
|
Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors)
Progressive disease (PD)
|
5 participants
|
1 participants
|
|
Tumor Response Assessment for Measurable Lesions According to RECIST, v1.1 (Response Evaluation Criteria in Solid Tumors)
Not evaluable
|
0 participants
|
0 participants
|
Adverse Events
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment
Serious events: 9 serious events
Other events: 18 other events
Deaths: 0 deaths
Regorafenib(Stivarga,BAY73-4506)-Severe Renal Impairment
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment
n=18 participants at risk
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
n=6 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Stress cardiomyopathy
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Intestinal obstruction
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Pancreatitis
|
5.6%
1/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
11.1%
2/18 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Chest pain
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Renal and urinary disorders
Haematuria
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Vascular disorders
Deep vein thrombosis
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Vascular disorders
Embolism
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
Other adverse events
| Measure |
Regorafenib(Stivarga, BAY73-4506)-Normal/Mild Impairment
n=18 participants at risk
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
n=6 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.1%
2/18 • Number of events 6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 5 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Cardiac disorders
Angina pectoris
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Cardiac disorders
Tachycardia
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Ear and labyrinth disorders
Ear discomfort
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Eye disorders
Cataract
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Eye disorders
Chalazion
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Eye disorders
Eye pain
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Eye disorders
Glaucoma
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Eye disorders
Vision blurred
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Abdominal distension
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Abdominal pain
|
27.8%
5/18 • Number of events 12 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
50.0%
3/6 • Number of events 6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Abdominal pain lower
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Cheilitis
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
50.0%
3/6 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Constipation
|
27.8%
5/18 • Number of events 7 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
50.0%
3/6 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Diarrhoea
|
44.4%
8/18 • Number of events 16 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
66.7%
4/6 • Number of events 12 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Diverticulum
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Dry mouth
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Dyspepsia
|
22.2%
4/18 • Number of events 6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Eructation
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Faecal incontinence
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Faecaloma
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Flatulence
|
11.1%
2/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
16.7%
3/18 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Glossodynia
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Haematemesis
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Inguinal hernia
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Lip ulceration
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Nausea
|
55.6%
10/18 • Number of events 20 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
100.0%
6/6 • Number of events 8 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Odynophagia
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Stomatitis
|
16.7%
3/18 • Number of events 6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 8 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Toothache
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
6/18 • Number of events 8 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
66.7%
4/6 • Number of events 9 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Asthenia
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Chest pain
|
16.7%
3/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Chills
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Drug intolerance
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Early satiety
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Fatigue
|
72.2%
13/18 • Number of events 24 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
50.0%
3/6 • Number of events 7 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Impaired healing
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Medical device site reaction
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Mucosal inflammation
|
22.2%
4/18 • Number of events 14 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Oedema
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Oedema peripheral
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Pyrexia
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
General disorders
Vessel puncture site bruise
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Infections and infestations
Candida infection
|
16.7%
3/18 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Infections and infestations
Cellulitis
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Infections and infestations
Eye infection
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Infections and infestations
Pneumonia
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Infections and infestations
Sinusitis
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Infections and infestations
Subcutaneous abscess
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Infections and infestations
Urinary tract infection
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Injury, poisoning and procedural complications
Contusion
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Injury, poisoning and procedural complications
Face injury
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Injury, poisoning and procedural complications
Fall
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Injury, poisoning and procedural complications
Procedural site reaction
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Injury, poisoning and procedural complications
Subcutaneous haematoma
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Alanine aminotransferase increased
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Amylase increased
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 8 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Aspartate aminotransferase increased
|
5.6%
1/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Blood bilirubin increased
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Blood creatinine increased
|
11.1%
2/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Blood fibrinogen decreased
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Blood urea increased
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Cardiac murmur
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
International normalised ratio increased
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Lipase increased
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 10 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Troponin increased
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Investigations
Weight decreased
|
33.3%
6/18 • Number of events 9 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Decreased appetite
|
61.1%
11/18 • Number of events 23 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
50.0%
3/6 • Number of events 5 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Dehydration
|
16.7%
3/18 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Hyperlipasaemia
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.6%
1/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.6%
1/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Metabolism and nutrition disorders
Lactose intolerance
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
27.8%
5/18 • Number of events 15 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
50.0%
3/6 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
22.2%
4/18 • Number of events 6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
33.3%
6/18 • Number of events 14 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
11.1%
2/18 • Number of events 6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
11.1%
2/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
33.3%
6/18 • Number of events 15 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Neck mass
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.6%
1/18 • Number of events 5 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Nervous system disorders
Disturbance in attention
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Nervous system disorders
Dizziness
|
22.2%
4/18 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Nervous system disorders
Dysgeusia
|
16.7%
3/18 • Number of events 4 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Nervous system disorders
Headache
|
55.6%
10/18 • Number of events 18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 5 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Nervous system disorders
Neuropathy peripheral
|
11.1%
2/18 • Number of events 7 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Nervous system disorders
Sensory disturbance
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Psychiatric disorders
Agitation
|
5.6%
1/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Psychiatric disorders
Anxiety
|
5.6%
1/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Psychiatric disorders
Insomnia
|
16.7%
3/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Renal and urinary disorders
Dysuria
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Renal and urinary disorders
Proteinuria
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
50.0%
3/6 • Number of events 6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Renal and urinary disorders
Urinary retention
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Reproductive system and breast disorders
Menstruation irregular
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Reproductive system and breast disorders
Pelvic pain
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.2%
4/18 • Number of events 5 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
44.4%
8/18 • Number of events 12 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 9 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
33.3%
6/18 • Number of events 8 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
16.7%
3/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.6%
1/18 • Number of events 7 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.6%
1/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
22.2%
4/18 • Number of events 7 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Palmar erythema
|
5.6%
1/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
55.6%
10/18 • Number of events 32 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
50.0%
3/6 • Number of events 15 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.1%
2/18 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Rash
|
27.8%
5/18 • Number of events 12 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
33.3%
2/6 • Number of events 3 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/18 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Skin and subcutaneous tissue disorders
Swelling face
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Vascular disorders
Flushing
|
5.6%
1/18 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Vascular disorders
Hot flush
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
0.00%
0/6 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Vascular disorders
Hypertension
|
44.4%
8/18 • Number of events 10 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
66.7%
4/6 • Number of events 10 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
|
Vascular disorders
Hypotension
|
11.1%
2/18 • Number of events 2 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
16.7%
1/6 • Number of events 1 • From start of study treatment until 30 days after last dose of study medication.
Safety was assessed routinely and on an ongoing basis
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60