Trial Outcomes & Findings for Phase I Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Participants With Colorectal Cancer (MK-0646-016) (NCT NCT00925015)
NCT ID: NCT00925015
Last Updated: 2018-08-15
Results Overview
To be declared a DLT an adverse experience had a causality related to study therapy. DLTs could be adverse experiences possibly, probably, or definitely related to study therapy by the Investigator, and included the following : Grade 4 neutropenia lasting \>= 5 days; Grade 3 or 4 neutropenia with fever \>38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except inadequately treated diarrhea, nausea and vomiting, rash, hyperglycemia, and transient abnormality of electrolytes. Anemia, infusion reactions, hypersensitivity reactions, and adverse experiences not-related to study therapy did not qualify as DLTs.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome timeframe
Four weeks of Cycle 1 treatment (up to 28 days)
Results posted on
2018-08-15
Participant Flow
Participant milestones
| Measure |
Cetux/Irin - Dmab 10 mg/kg
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in Cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1, 8, 15, 22, 29 and 36. Each cycle was 6 weeks long.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. Each cycle was 6 weeks long. For Drug-Drug Interaction (DDI).
|
|---|---|---|---|
|
Overall Study
STARTED
|
8
|
6
|
6
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
8
|
6
|
6
|
Reasons for withdrawal
| Measure |
Cetux/Irin - Dmab 10 mg/kg
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in Cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1, 8, 15, 22, 29 and 36. Each cycle was 6 weeks long.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. Each cycle was 6 weeks long. For Drug-Drug Interaction (DDI).
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
2
|
1
|
|
Overall Study
Physician Decision
|
0
|
1
|
0
|
|
Overall Study
Progressive Disease
|
7
|
3
|
4
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
Baseline Characteristics
Phase I Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Participants With Colorectal Cancer (MK-0646-016)
Baseline characteristics by cohort
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=8 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in Cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1, 8, 15, 22, 29 and 36. Each cycle was 6 weeks long.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
n=6 Participants
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. Each cycle was 6 weeks long. For Drug-Drug Interaction (DDI).
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
62.3 Years
STANDARD_DEVIATION 5.6 • n=99 Participants
|
59.3 Years
STANDARD_DEVIATION 3.6 • n=107 Participants
|
59.7 Years
STANDARD_DEVIATION 8.5 • n=206 Participants
|
60.6 Years
STANDARD_DEVIATION 6.0 • n=7 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Four weeks of Cycle 1 treatment (up to 28 days)Population: Participants treated with study medication. The Dmab 10 mg/kg - Cetux/Irin arm was not evaluated. In the Cetux/Irin - Dmab 10 mg/kg (DDI) arm two participants were not analyzed because one had febrile neutropenia (Grade 3) before the first treatment, and the second had a skin toxicity (Grade 3) before the DLT evaluation period.
To be declared a DLT an adverse experience had a causality related to study therapy. DLTs could be adverse experiences possibly, probably, or definitely related to study therapy by the Investigator, and included the following : Grade 4 neutropenia lasting \>= 5 days; Grade 3 or 4 neutropenia with fever \>38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except inadequately treated diarrhea, nausea and vomiting, rash, hyperglycemia, and transient abnormality of electrolytes. Anemia, infusion reactions, hypersensitivity reactions, and adverse experiences not-related to study therapy did not qualify as DLTs.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=6 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Number of Dose-limiting Toxicities (DLTs)
|
0 DLT
|
1 DLT
|
—
|
PRIMARY outcome
Timeframe: Approximately 4 weeks after last drug treatment (up to Day 293)Population: Participants treated with study medication.
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=8 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
n=6 Participants
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Number of Participants With an Adverse Event (AE)
|
8 Participants
|
6 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Up to 12 weeks after the last administration of dalotuzumab (up to 349 days)Population: All treated participants, excluding those without measurable data.
Sera were collected from participants prior to administration of the first dose of study drug, every 6 weeks during the study period, then 4 weeks, 8 weeks and 12 weeks post-treatment. A sandwich format enzyme-linked immunosorbent assay (ELISA) was used to detect the presence of HAHA in serum.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=8 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
n=6 Participants
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Number of Participants With Human Anti-Human Antibody (HAHA)
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusionPopulation: Participants from the Dmab 10 mg/kg - Cetux/Irin (DDI) arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Tmax of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=6 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Time to Maximum Concentration (Tmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone in or in Combination With Cetuximab / Irinotecan
|
5.0 h
Interval 2.0 to 8.0
|
3.5 h
Interval 2.0 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusionPopulation: Participants from the Dmab 10 mg/kg - Cetux/Irin (DDI) arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Ceoi of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=6 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Concentration at the End of Infusion (Ceoi) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
|
211.2 µg/mL
Geometric Coefficient of Variation 14.3 • Interval 2.0 to 8.0
|
267.3 µg/mL
Geometric Coefficient of Variation 27.1 • Interval 2.0 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusionPopulation: Participants from the Dmab 10 mg/kg - Cetux/Irin (DDI) arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Cmax of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=6 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Maximum Concentration (Cmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
|
247.6 µg/mL
Geometric Coefficient of Variation 14.4 • Interval 2.0 to 8.0
|
311.9 µg/mL
Geometric Coefficient of Variation 21.3 • Interval 2.0 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusionPopulation: Participants from the Dmab 10 mg/kg - Cetux/Irin (DDI) arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The T1/2 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=6 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Apparent Terminal Half-life (T1/2) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
|
131.4 h
Geometric Coefficient of Variation 21.5 • Interval 2.0 to 8.0
|
141.4 h
Geometric Coefficient of Variation 32.1 • Interval 2.0 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusionPopulation: Participants from the Dmab 10 mg/kg - Cetux/Irin (DDI) arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The CL of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=6 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Clearance From Plasma (CL) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
|
0.0049 mL/min/kg
Geometric Coefficient of Variation 21.9 • Interval 2.0 to 8.0
|
0.0038 mL/min/kg
Geometric Coefficient of Variation 33.7 • Interval 2.0 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusionPopulation: Participants from the Dmab 10 mg/kg - Cetux/Irin (DDI) arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Vss of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=6 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Steady-state Volume of Distribution (Vss) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
|
0.0558 L/kg
Geometric Coefficient of Variation 11.1 • Interval 2.0 to 8.0
|
0.0459 L/kg
Geometric Coefficient of Variation 14.2 • Interval 2.0 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8 and 24 h after initiation of dalotuzumab infusionPopulation: Participants from the Dmab 10 mg/kg - Cetux/Irin (DDI) arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The AUC0-24 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=6 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve From 0-24 Hours Post-dose (AUC0-24) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
|
4.56 mg*h/mL
Geometric Coefficient of Variation 11.7 • Interval 2.0 to 8.0
|
5.39 mg*h/mL
Geometric Coefficient of Variation 18.8 • Interval 2.0 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusionPopulation: Participants from the Dmab 10 mg/kg - Cetux/Irin (DDI) arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The AUC0-168 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=6 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve From 0-168 Hours Post-dose (AUC0-168) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
|
19.6 mg*h/mL
Geometric Coefficient of Variation 13.1 • Interval 2.0 to 8.0
|
24.5 mg*h/mL
Geometric Coefficient of Variation 19.0 • Interval 2.0 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m\^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m\^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Tmax of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Tmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
7.9 h
Interval 2.0 to 8.0
|
2.0 h
Interval 2.0 to 2.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m\^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m\^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Cmax of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Cmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
204.0 µg/mL
Geometric Coefficient of Variation 15.0 • Interval 2.0 to 8.0
|
236.5 µg/mL
Geometric Coefficient of Variation 23.0 • Interval 2.0 to 2.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m\^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m\^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The T1/2 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
T1/2 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
129.4 h
Geometric Coefficient of Variation 26.0 • Interval 2.0 to 8.0
|
131.9 h
Geometric Coefficient of Variation 34.5 • Interval 2.0 to 2.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m\^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m\^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The CL of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
CL of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
7.81 mL/h/m^2
Geometric Coefficient of Variation 32.8 • Interval 2.0 to 8.0
|
6.82 mL/h/m^2
Geometric Coefficient of Variation 40.5 • Interval 2.0 to 2.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m\^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m\^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Vss of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Vss of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
1.45 L/m^2
Geometric Coefficient of Variation 10.0 • Interval 2.0 to 8.0
|
1.32 L/m^2
Geometric Coefficient of Variation 17.8 • Interval 2.0 to 2.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8 and 24 h after initiation of cetuximab infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m\^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m\^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The AUC0-24 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
AUC0-24 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
4.02 mg*h/mL
Geometric Coefficient of Variation 14.5 • Interval 2.0 to 8.0
|
4.12 mg*h/mL
Geometric Coefficient of Variation 26.1 • Interval 2.0 to 2.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m\^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m\^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The AUC0-168 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
AUC0-168 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
18.6 mg*h/mL
Geometric Coefficient of Variation 20.9 • Interval 2.0 to 8.0
|
20.1 mg*h/mL
Geometric Coefficient of Variation 28.6 • Interval 2.0 to 2.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m\^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Tmax of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Tmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
1.0 h
Interval 0.97 to 1.0
|
1.0 h
Interval 1.0 to 1.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m\^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Cmax of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Cmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
1.21 µg/mL
Geometric Coefficient of Variation 22.8 • Interval 0.97 to 1.0
|
1.13 µg/mL
Geometric Coefficient of Variation 25.6 • Interval 1.0 to 1.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m\^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The T1/2 of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29..
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
T1/2 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
8.95 h
Geometric Coefficient of Variation 9.13 • Interval 0.97 to 1.0
|
9.67 h
Geometric Coefficient of Variation 12.7 • Interval 1.0 to 1.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m\^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The CL of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
CL of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
12.3 L/h/m^2
Geometric Coefficient of Variation 35.7 • Interval 0.97 to 1.0
|
13.1 L/h/m^2
Geometric Coefficient of Variation 34.3 • Interval 1.0 to 1.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m\^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Vss of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
Vss of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
117 L/m^2
Geometric Coefficient of Variation 27.5 • Interval 0.97 to 1.0
|
137 L/m^2
Geometric Coefficient of Variation 24.9 • Interval 1.0 to 1.1
|
—
|
SECONDARY outcome
Timeframe: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8 and 24 h after completion of Irinotecan infusionPopulation: Participants from the Cetux/Irin - Dmab 10 mg/kg arm only, who were treated with study medication and had evaluable measurements at baseline and at least once during treatment. No explicit imputation was made for missing data.
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m\^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The AUC0-24 of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Outcome measures
| Measure |
Cetux/Irin - Dmab 10 mg/kg
n=7 Participants
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1,8, 15, 22, 29 and 36.
|
Cetux/Irin - Dmab 15/7.5 mg/kg
n=6 Participants
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Day 8; followed in subsequent infusions by treatment with 7.5 mg/kg on Days 22 and 36. Each cycle was 6 weeks long.
|
Dmab 10 mg/kg - Cetux/Irin (DDI)
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For DDI.
|
|---|---|---|---|
|
AUC0-24 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
|
7.19 µg*h/mL
Geometric Coefficient of Variation 33.6 • Interval 0.97 to 1.0
|
6.64 µg*h/mL
Geometric Coefficient of Variation 31.9 • Interval 1.0 to 1.1
|
—
|
Adverse Events
Cetux/Irin - Dalotuzumab 10 mg/Kg
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Cetux/Irin - Dalotuzumab 15/7.5 mg/Kg
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Dalotuzumab 10 mg/Kg - Cetux/Irin (DDI)
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cetux/Irin - Dalotuzumab 10 mg/Kg
n=8 participants at risk
After treatment with Cetux and Irin, Dmab was administered as an intravenous infusion at 10 mg/kg in Cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1, 8, 15, 22, 29 and 36. Each cycle was 6 weeks long.
|
Cetux/Irin - Dalotuzumab 15/7.5 mg/Kg
n=6 participants at risk
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Days 8, 22 and 36; followed in subsequent cycles by treatment with 7.5 mg/kg on Days 8, 22 and 36. Each cycle was 6 weeks long.
|
Dalotuzumab 10 mg/Kg - Cetux/Irin (DDI)
n=6 participants at risk
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. Each cycle was 6 weeks long.
|
|---|---|---|---|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
General disorders
Pyrexia
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
Other adverse events
| Measure |
Cetux/Irin - Dalotuzumab 10 mg/Kg
n=8 participants at risk
After treatment with Cetux and Irin, Dmab was administered as an intravenous infusion at 10 mg/kg in Cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1, 8, 15, 22, 29 and 36. Each cycle was 6 weeks long.
|
Cetux/Irin - Dalotuzumab 15/7.5 mg/Kg
n=6 participants at risk
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Days 8, 22 and 36; followed in subsequent cycles by treatment with 7.5 mg/kg on Days 8, 22 and 36. Each cycle was 6 weeks long.
|
Dalotuzumab 10 mg/Kg - Cetux/Irin (DDI)
n=6 participants at risk
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. Each cycle was 6 weeks long.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
25.0%
2/8 • Number of events 4 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Blood and lymphatic system disorders
Leukopenia
|
87.5%
7/8 • Number of events 24 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 4 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
100.0%
6/6 • Number of events 18 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
50.0%
4/8 • Number of events 17 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Blood and lymphatic system disorders
Neutropenia
|
87.5%
7/8 • Number of events 24 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 4 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
83.3%
5/6 • Number of events 27 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
37.5%
3/8 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Cardiac disorders
Arrhythmia
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Constipation
|
37.5%
3/8 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
37.5%
3/8 • Number of events 7 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
83.3%
5/6 • Number of events 23 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 18 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Nausea
|
62.5%
5/8 • Number of events 8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
66.7%
4/6 • Number of events 8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Periodontal disease
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Plicated tongue
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Stomatitis
|
62.5%
5/8 • Number of events 7 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
General disorders
Fatigue
|
50.0%
4/8 • Number of events 8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
66.7%
4/6 • Number of events 9 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
General disorders
Infusion related reaction
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
General disorders
Mucosal inflammation
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
General disorders
Oedema
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
General disorders
Pain
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
General disorders
Pyrexia
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
12.5%
1/8 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Infections and infestations
Cystitis
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Infections and infestations
Infection
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Infections and infestations
Paronychia
|
75.0%
6/8 • Number of events 14 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
83.3%
5/6 • Number of events 16 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 4 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Investigations
Alanine aminotransferase increased
|
25.0%
2/8 • Number of events 9 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Investigations
Aspartate aminotransferase increased
|
37.5%
3/8 • Number of events 7 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 4 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Investigations
Blood alkaline phosphatase increased
|
37.5%
3/8 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Investigations
Blood creatine phosphokinase increased
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Investigations
Blood creatinine increased
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Investigations
Blood lactate dehydrogenase increased
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Investigations
C-reactive protein increased
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Investigations
Gamma-glutamyltransferase increased
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Investigations
Weight decreased
|
62.5%
5/8 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
50.0%
4/8 • Number of events 8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 9 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
25.0%
2/8 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 9 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
50.0%
4/8 • Number of events 4 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
25.0%
2/8 • Number of events 4 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 7 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 7 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
12.5%
1/8 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
25.0%
2/8 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Musculoskeletal and connective tissue disorders
Hypercreatinaemia
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Nervous system disorders
Dysgeusia
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Nervous system disorders
Headache
|
12.5%
1/8 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Psychiatric disorders
Insomnia
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Renal and urinary disorders
Proteinuria
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
66.7%
4/6 • Number of events 12 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
2/8 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
87.5%
7/8 • Number of events 20 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
83.3%
5/6 • Number of events 12 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
25.0%
2/8 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
50.0%
3/6 • Number of events 5 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
12.5%
1/8 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
12.5%
1/8 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
25.0%
2/8 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
33.3%
2/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.5%
1/8 • Number of events 4 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Skin erosion
|
25.0%
2/8 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
12.5%
1/8 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Skin and subcutaneous tissue disorders
Xeroderma
|
0.00%
0/8 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 2 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
|
Vascular disorders
Flushing
|
12.5%
1/8 • Number of events 3 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
16.7%
1/6 • Number of events 1 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
0.00%
0/6 • Approximately 4 weeks after last drug treatment (up to Day 293)
Participants treated with one or more doses of study medication.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
- Publication restrictions are in place
Restriction type: OTHER