Trial Outcomes & Findings for A Phase Ib, Open-label, Multicenter Study of the Safety and PK of the Combination of rhuMAb2c4 (Omnitarg), a Recombinant Humanized Antibody to HER2, and Capecitabine (Xeloda) in Patients With Advanced Solid Tumors (NCT NCT02494596)
NCT ID: NCT02494596
Last Updated: 2015-11-10
Results Overview
MTD was defined as the highest tolerated dose combination of capecitabine (825 mg, 1000 mg or 1250 mg) and pertuzumab, without causing Dose Limiting Toxicities (DLTs). DLTs were defined as follows: 1) Any non-hematological toxicity greater than or equal to (≥) Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management; 2) Grade 4 neutropenia lasting \> 7 days; 3) Febrile neutropenia; 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion; 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. Participants who withdrew from the study without completing the first treatment cycle for reasons other than DLT were not considered evaluable for DLT. MTD was measured in mg/m\^2.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
19 participants
Primary outcome timeframe
Cycle 1 (3 Weeks)
Results posted on
2015-11-10
Participant Flow
Participants were grouped into three cohorts and received either 825 mg, 1000 mg or 1250 mg capecitabine to determine the maximum tolerated dose.
Participant milestones
| Measure |
Capecitabine 825 Plus (+) Pertuzumab 1050
Participants received a single dose of capecitabine 825 milligrams per square meter (mg/m\^2) orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg intravenous (IV) infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Overall Study
STARTED
|
5
|
7
|
7
|
|
Overall Study
COMPLETED
|
2
|
2
|
6
|
|
Overall Study
NOT COMPLETED
|
3
|
5
|
1
|
Reasons for withdrawal
| Measure |
Capecitabine 825 Plus (+) Pertuzumab 1050
Participants received a single dose of capecitabine 825 milligrams per square meter (mg/m\^2) orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg intravenous (IV) infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Overall Study
Insufficient Therapeutic Response
|
3
|
3
|
1
|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
|
Overall Study
Refused Treatment
|
0
|
1
|
0
|
Baseline Characteristics
A Phase Ib, Open-label, Multicenter Study of the Safety and PK of the Combination of rhuMAb2c4 (Omnitarg), a Recombinant Humanized Antibody to HER2, and Capecitabine (Xeloda) in Patients With Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
Capecitabine + Pertuzumab
n=18 Participants
Participants received a single dose of capecitabine either 825, 1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|
|
Age, Continuous
|
60.9 years
STANDARD_DEVIATION 9.10 • n=93 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (3 Weeks)Population: The Safety Population included all participants who received any amount of study medication and who had at least one post-baseline safety follow-up.
MTD was defined as the highest tolerated dose combination of capecitabine (825 mg, 1000 mg or 1250 mg) and pertuzumab, without causing Dose Limiting Toxicities (DLTs). DLTs were defined as follows: 1) Any non-hematological toxicity greater than or equal to (≥) Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management; 2) Grade 4 neutropenia lasting \> 7 days; 3) Febrile neutropenia; 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion; 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. Participants who withdrew from the study without completing the first treatment cycle for reasons other than DLT were not considered evaluable for DLT. MTD was measured in mg/m\^2.
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=18 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Maximum Tolerated Dose (MTD) of the Combination of Pertuzumab and Capecitabine
|
1250 mg/m^2
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 (3 Weeks)Population: Safety population
DLTs were defined as follows: 1)Any non-hematological toxicity greater than or equal to (≥) Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management; 2) Grade 4 neutropenia lasting \> 7 days; 3) Febrile neutropenia; 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion; 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. Participants who withdrew from the study without completing the first treatment cycle for reasons other than DLT were not considered evaluable for DLT.
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=5 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
n=6 Participants
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
n=7 Participants
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Percentage of Participants With DLTs
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and Predose on Days 8, 15 and 22Population: ITT population
The biological half-life or terminal half-life of pertuzumab is the time in days it takes for it to lose half of its pharmacologic activity. t1/2 was measured in days.
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=18 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Plasma Half-Life (t1/2) of Pertuzumab
|
14.6 days
Standard Deviation 41.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22Population: ITT population
Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and was measured as nanograms per milliliter (ng/mL).
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=18 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Pertuzumab
|
355111 ng/mL
Standard Deviation 59051
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22Population: ITT population
Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination. Tmax was measured in days.
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=18 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) of Pertuzumab
|
0.137 days
Standard Deviation 0.076
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22Population: ITT population
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC was measured as ng\*day/mL.
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=18 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Area Under the Concentration Curve From Time Zero to Last Measurement (AUC 0-last) of Pertuzumab
|
2742561 ng*day/mL
Standard Deviation 743598
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22Population: ITT population
The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as nanograms times days per milliliter (ng\*day/mL).
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=18 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
AUC From Time Zero to Infinity (AUC 0-infinity) of Pertuzumab
|
4096501 ng*day/mL
Standard Deviation 1282130
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22Population: ITT population
The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. Vss was measured in mL
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=18 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Apparent Volume of Distribution of Pertuzumab
|
5202 mL
Standard Deviation 1007
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Days 2, 5, 8 and 15 Postdose; Cycle 2: Day 1 at drug administration, predose and 15 minutes postdose, and predose on Days 8, 15 and 22Population: ITT population
Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day).
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=18 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Apparent Total Clearance of Pertuzumab
|
283.0 mL/day
Standard Deviation 98.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day -7: Predose, 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours postdose; Cycle 1 Day 1: Predose, 0 and 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours PostdosePopulation: ITT population
Capecitabine is a novel oral fluoropyrimidine carbamate that is preferentially converted to the cytotoxic moiety fluorouracil (5-fluorouracil; 5-FU) in target tumour tissue through a series of 3 metabolic steps through the intermediate metabolites 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR), and α-fluoro-β-alanine (FBAL). The biological half-life or terminal half-life is the time in days it takes for it to lose half of its pharmacologic activity.
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=5 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
n=6 Participants
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
n=7 Participants
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone 5'-DFCR
|
0.89 hours
Standard Deviation 0.27
|
0.82 hours
Standard Deviation 0.28
|
0.82 hours
Standard Deviation 0.23
|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone 5'-DFUR
|
0.75 hours
Standard Deviation 0.26
|
0.76 hours
Standard Deviation 0.23
|
0.66 hours
Standard Deviation 0.09
|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone 5-FU
|
0.67 hours
Standard Deviation 0.22
|
0.64 hours
Standard Deviation 0.13
|
0.70 hours
Standard Deviation 0.16
|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone Capecitabine
|
0.54 hours
Standard Deviation 0.19
|
0.40 hours
Standard Deviation 0.10
|
0.36 hours
Standard Deviation 0.11
|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone FBAL
|
2.54 hours
Standard Deviation 0.30
|
2.69 hours
Standard Deviation 0.39
|
3.08 hours
Standard Deviation 0.78
|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab 5'-DFCR
|
0.78 hours
Standard Deviation 0.38
|
0.76 hours
Standard Deviation 0.18
|
0.75 hours
Standard Deviation 0.14
|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab 5'-DFUR
|
0.62 hours
Standard Deviation 0.13
|
0.73 hours
Standard Deviation 0.21
|
0.79 hours
Standard Deviation 0.28
|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab 5-FU
|
0.73 hours
Standard Deviation 0.40
|
0.67 hours
Standard Deviation 0.14
|
0.80 hours
Standard Deviation 0.35
|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab Capecitabine
|
0.42 hours
Standard Deviation 0.14
|
0.62 hours
Standard Deviation 0.28
|
0.54 hours
Standard Deviation 0.28
|
|
Plasma Half-Life of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab FBAL
|
2.59 hours
Standard Deviation 0.64
|
2.58 hours
Standard Deviation 0.57
|
2.81 hours
Standard Deviation 0.44
|
SECONDARY outcome
Timeframe: Day -7: Predose, 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours postdose; Cycle 1 Day 1: Predose, 0 and 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours PostdosePopulation: ITT population
Capecitabine is an oral fluoropyrimidine carbamate that is preferentially converted to the cytotoxic moiety 5-FU in target tumour tissue through a series of 3 metabolic steps through the intermediate metabolites 5'-DFCR, 5'-DFUR, and FBAL. Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as nanograms per milliliter (ng/mL).
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=5 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
n=6 Participants
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
n=7 Participants
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone 5'-DFCR
|
4508 ng/mL
Standard Deviation 2317
|
7687 ng/mL
Standard Deviation 1443
|
8647 ng/mL
Standard Deviation 3254
|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone 5'-DFUR
|
5274 ng/mL
Standard Deviation 1832
|
7657 ng/mL
Standard Deviation 2708
|
10311 ng/mL
Standard Deviation 3323
|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone 5-FU
|
201 ng/mL
Standard Deviation 94
|
355 ng/mL
Standard Deviation 119
|
369 ng/mL
Standard Deviation 107
|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone Capecitabine
|
4802 ng/mL
Standard Deviation 3159
|
9112 ng/mL
Standard Deviation 6189
|
7543 ng/mL
Standard Deviation 2944
|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone FBAL
|
3214 ng/mL
Standard Deviation 396
|
3963 ng/mL
Standard Deviation 947
|
5290 ng/mL
Standard Deviation 576
|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab 5'-DFCR
|
4909 ng/mL
Standard Deviation 2518
|
3917 ng/mL
Standard Deviation 1411
|
6569 ng/mL
Standard Deviation 2827
|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab 5'-DFUR
|
5736 ng/mL
Standard Deviation 1831
|
4103 ng/mL
Standard Deviation 1595
|
8683 ng/mL
Standard Deviation 4142
|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab 5-FU
|
219 ng/mL
Standard Deviation 106
|
187 ng/mL
Standard Deviation 92
|
345 ng/mL
Standard Deviation 214
|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab Capecitabine
|
8060 ng/mL
Standard Deviation 4800
|
3367 ng/mL
Standard Deviation 1741
|
4731 ng/mL
Standard Deviation 3198
|
|
Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab FBAL
|
3674 ng/mL
Standard Deviation 1121
|
3498 ng/mL
Standard Deviation 809
|
5136 ng/mL
Standard Deviation 843
|
SECONDARY outcome
Timeframe: Day -7: Predose, 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours postdose; Cycle 1 Day 1: Predose, 0 and 30 minutes, 1, 2, 3, 4, 5, 6 and 10 hours PostdosePopulation: ITT population
Capecitabine is a novel oral fluoropyrimidine carbamate that is preferentially converted to the cytotoxic moiety fluorouracil (5-fluorouracil; 5-FU) in target tumour tissue through a series of 3 metabolic steps through the intermediate metabolites 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR), and α-fluoro-β-alanine (FBAL). Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; when the rate of absorption equals the rate of elimination.
Outcome measures
| Measure |
Capecitabine + Pertuzumab
n=5 Participants
Participants received a single dose of capecitabine either 825,1000 or 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
n=6 Participants
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
n=7 Participants
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone 5'-DFCR
|
1.3 hours
Standard Deviation 0.66
|
0.82 hours
Standard Deviation 0.26
|
1.05 hours
Standard Deviation 0.51
|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone 5'-DFUR
|
1.3 hours
Standard Deviation 0.66
|
0.76 hours
Standard Deviation 0.49
|
1.05 hours
Standard Deviation 0.51
|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone 5-FU
|
1.3 hours
Standard Deviation 0.66
|
0.64 hours
Standard Deviation 0.49
|
1.05 hours
Standard Deviation 0.51
|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone Capecitabine
|
1.2 hours
Standard Deviation 0.75
|
0.4 hours
Standard Deviation 0.28
|
0.77 hours
Standard Deviation 0.35
|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine Alone FBAL
|
2.4 hours
Standard Deviation 0.55
|
2.69 hours
Standard Deviation 0.41
|
2.21 hours
Standard Deviation 0.40
|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab 5'-DFCR
|
0.9 hours
Standard Deviation 0.65
|
1.42 hours
Standard Deviation 0.66
|
1.86 hours
Standard Deviation 1.32
|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab 5'-DFUR
|
1.0 hours
Standard Deviation 0.61
|
2.0 hours
Standard Deviation 1.10
|
1.86 hours
Standard Deviation 1.32
|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab 5-FU
|
0.9 hours
Standard Deviation 0.65
|
1.84 hours
Standard Deviation 1.17
|
1.93 hours
Standard Deviation 1.24
|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab Capecitabine
|
0.7 hours
Standard Deviation 0.28
|
1.17 hours
Standard Deviation 0.40
|
1.15 hours
Standard Deviation 0.62
|
|
Time to Maximum Plasma Concentration of Capecitabine and it's Metabolites When Given Alone and in Combination With Pertuzumab
Capecitabine + Pertuzumab FBAL
|
2.6 hours
Standard Deviation 0.90
|
3.16 hours
Standard Deviation 1.17
|
2.50 hours
Standard Deviation 1.39
|
Adverse Events
Capecitabine 825 + Pertuzumab 1050
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Capecitabine 1000 + Pertuzumab 1050
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Capecitabine 1250 + Pertuzumab 1050
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Capecitabine 825 + Pertuzumab 1050
n=5 participants at risk
Participants received a single dose of capecitabine 825 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
n=6 participants at risk
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
n=7 participants at risk
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
Other adverse events
| Measure |
Capecitabine 825 + Pertuzumab 1050
n=5 participants at risk
Participants received a single dose of capecitabine 825 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1000 + Pertuzumab 1050
n=6 participants at risk
Participants received a single dose of capecitabine 1000 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
Capecitabine 1250 + Pertuzumab 1050
n=7 participants at risk
Participants received a single dose of capecitabine 1250 mg/m\^2 orally on Day -7 and subsequently on Days 1 to 14 of each 3-week cycle administered twice daily. Participants also received pertuzumab on Day 1 of each 3-week cycle as a fixed-dose of 1050-mg IV infusion until progression of the disease, occurrence of unacceptable toxicity or withdrawal of consent.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
60.0%
3/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
50.0%
3/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
100.0%
7/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Nausea
|
80.0%
4/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
66.7%
4/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
57.1%
4/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
2/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
50.0%
3/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
28.6%
2/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
33.3%
2/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
28.6%
2/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
42.9%
3/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Haemorrhoids
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Glossitis
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Lip dry
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Odynophagia
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Gastrointestinal disorders
Toothache
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
General disorders
Asthenia
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
50.0%
3/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
57.1%
4/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
33.3%
2/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
57.1%
4/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
General disorders
Pyrexia
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
33.3%
2/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
28.6%
2/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
General disorders
Oedema Peripheral
|
40.0%
2/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
General disorders
Catheter site pain
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
General disorders
Chest pain
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
General disorders
Chills
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
General disorders
Feeling hot
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Metabolism and nutrition disorders
Anorexia
|
40.0%
2/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
50.0%
3/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
57.1%
4/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Nervous system disorders
Lethargy
|
40.0%
2/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
33.3%
2/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
28.6%
2/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
28.6%
2/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Nervous system disorders
Dysgeusia
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Skin and subcutaneous tissue disorders
Skin reaction
|
40.0%
2/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
28.6%
2/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
42.9%
3/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
33.3%
2/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Infections and infestations
Influenza
|
40.0%
2/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
28.6%
2/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
28.6%
2/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
42.9%
3/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Psychiatric disorders
Depressed mood
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Psychiatric disorders
Anxiety
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Psychiatric disorders
Confusional state
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Musculoskeletal and connective tissue disorders
Ligament disorder
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Eye disorders
Keratoconjunctivitis sicca
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
57.1%
4/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Investigations
Blood bilirubin increased
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Investigations
Haematocrit decreased
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Renal and urinary disorders
Micturition disorder
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Renal and urinary disorders
Pollakiuria
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Vascular disorders
Hypotension
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
16.7%
1/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Reproductive system and breast disorders
Metrorrhagia
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
14.3%
1/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
|
Reproductive system and breast disorders
Pelvic pain
|
20.0%
1/5 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/6 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
0.00%
0/7 • Adverse events were recorded continuously from Day -7 until 4 weeks after the final visit.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER