Trial Outcomes & Findings for A Study for Participants With Pancreatic Cancer (NCT NCT00839332)
NCT ID: NCT00839332
Last Updated: 2018-04-17
Results Overview
The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after gemcitabine was based on the maximum tolerated dose and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity \[AUC(0-inf)\] \>21,000 nanogram\*hour/milliliter \[ng\*h/mL\] and maximum LY2603618 plasma concentration \[Cmax\] \>2000 nanograms/milliliter \[ng/mL\]).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
157 participants
Primary outcome timeframe
Baseline through 18 months
Results posted on
2018-04-17
Participant Flow
Participant milestones
| Measure |
Phase 1: LY2603618 + Gemcitabine
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70 to 250 milligrams/meter squared (mg/m\^2) LY2603618 as a 1-hour continuous intravenous (IV) infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: LY2603618 + Gemcitabine
LY2603618: 230 mg flat dose LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
Gemcitabine: Participants were administered 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|---|
|
Phase 1
STARTED
|
50
|
0
|
0
|
|
Phase 1
Received at Least 1 Dose of Study Drug
|
50
|
0
|
0
|
|
Phase 1
COMPLETED
|
0
|
0
|
0
|
|
Phase 1
NOT COMPLETED
|
50
|
0
|
0
|
|
Phase 2
STARTED
|
0
|
68
|
39
|
|
Phase 2
Received at Least 1 Dose of Study Drug
|
0
|
65
|
34
|
|
Phase 2
COMPLETED
|
0
|
0
|
0
|
|
Phase 2
NOT COMPLETED
|
0
|
68
|
39
|
Reasons for withdrawal
| Measure |
Phase 1: LY2603618 + Gemcitabine
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70 to 250 milligrams/meter squared (mg/m\^2) LY2603618 as a 1-hour continuous intravenous (IV) infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: LY2603618 + Gemcitabine
LY2603618: 230 mg flat dose LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
Gemcitabine: Participants were administered 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|---|
|
Phase 1
Disease Progression
|
38
|
0
|
0
|
|
Phase 1
Adverse Event
|
6
|
0
|
0
|
|
Phase 1
Withdrawal by Subject
|
4
|
0
|
0
|
|
Phase 1
Physician Decision
|
2
|
0
|
0
|
|
Phase 2
Protocol Violation
|
0
|
1
|
0
|
|
Phase 2
Disease Progression
|
0
|
46
|
21
|
|
Phase 2
Adverse Event
|
0
|
8
|
6
|
|
Phase 2
Death
|
0
|
4
|
2
|
|
Phase 2
Withdrawal by Subject
|
0
|
5
|
8
|
|
Phase 2
Physician Decision
|
0
|
4
|
1
|
|
Phase 2
Lost to Follow-up
|
0
|
0
|
1
|
Baseline Characteristics
A Study for Participants With Pancreatic Cancer
Baseline characteristics by cohort
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=50 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70 to 250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: LY2603618 + Gemcitabine
n=65 Participants
LY2603618: 230 mg flat dose LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
Gemcitabine: Participants were administered 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
n=34 Participants
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
Total
n=149 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
59.0 years
STANDARD_DEVIATION 12.2 • n=5 Participants
|
64.3 years
STANDARD_DEVIATION 8.3 • n=7 Participants
|
64.4 years
STANDARD_DEVIATION 10.1 • n=5 Participants
|
62.54 years
STANDARD_DEVIATION 11.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
61 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
88 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
46 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
140 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
32 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
73 Participants
n=4 Participants
|
|
Region of Enrollment
Spain
|
18 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
|
Region of Enrollment
Romania
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Region of Enrollment
Germany
|
0 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
|
Region of Enrollment
Netherlands
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Region of Enrollment
Italy
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Region of Enrollment
Poland
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Pancreas
|
10 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
109 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Colon
|
7 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Breast
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Non-Small Cell, Lung NOS
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Cervix
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Rectum
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Endometrium
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Infiltrating Ductal, Breast
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Renal Cell
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Sarcoma, Leiomyosarcoma, Abdomen (Non-Gist)
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Squamous Cell Carcinoma, Head and Neck
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Ampulla of Pancreas
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Head and Neck
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Ovarian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Peritoneal
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Small Cell, Lung
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Carcinoma, Transitional Cell, Urothelium
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Ewing's Sarcoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Lymphoma, Non-Hodgkin's Lymphoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Mesothelioma, Pleural, Malignant
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Ovarian Adenocarcinoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Squamous Cell Carcinoma, Cervix
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Initial Pathological Diagnosis
Tumor
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG Status 0
|
19 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
61 Participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG Status 1
|
31 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
79 Participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG Status 2
|
0 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline through 18 monthsPopulation: Phase 1 participants who received at least 1 dose of study drug.
The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after gemcitabine was based on the maximum tolerated dose and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity \[AUC(0-inf)\] \>21,000 nanogram\*hour/milliliter \[ng\*h/mL\] and maximum LY2603618 plasma concentration \[Cmax\] \>2000 nanograms/milliliter \[ng/mL\]).
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=50 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 1: Determine the Recommended Phase 2 Dose for LY2603618 When Administered After Gemcitabine
|
230 milligrams (mg)
|
—
|
PRIMARY outcome
Timeframe: Phase 2: Baseline to date of deathPopulation: Phase 2 participants who were randomized.
Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the cut-off date. OS was summarized using Kaplan-Meier estimates.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=65 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
n=34 Participants
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 2: Overall Survival (OS)
|
7.8 months
Interval 5.0 to 11.1
|
8.3 months
Interval 5.1 to 14.1
|
SECONDARY outcome
Timeframe: Phase 1: LY2603618 - Predose and 0, 1, 3, 6, 24, 48, and 72 hours after the end of infusion on C1 /D2, C1 /D16, and C2 /D2. Gemcitabine - Predose and 0, 10, 30, 60, and 120 minutes after the end of infusion on C1 /D1, C1 /D15, and C2 /D1.Population: Phase 1 participants who received at least 1 dose of study drug (LY2603618) and had sufficient LY2603618 plasma concentration data to enable determination of the LY2603618 Cmax.
Plasma samples for pharmacokinetic (PK) analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine and dFdU plasma concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only the LY2603618 plasma Cmax values are reported for each LY2603618 dose level on Cycle (C) 1 /Day (D) 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each dose level and time point.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=50 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
70 mg/m^2, Cycle 1 /Day 2
|
3530 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
70 mg/m^2, Cycle 1 /Day 16
|
3360 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 26
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
70 mg/m^2, Cycle 2 /Day 2
|
3100 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 12
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
105 mg/m^2, Cycle 1 /Day 2
|
4890 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 25
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
105 mg/m^2, Cycle 1 /Day 16
|
5170 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 38
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
105 mg/m^2, Cycle 2 /Day 2
|
5360 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
150 mg/m^2, Cycle 1 /Day 2
|
4280 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 29
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
150 mg/m^2, Cycle 1 /Day 16
|
5040 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 38
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
150 mg/m^2, Cycle 2 /Day 2
|
4370 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 38
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
200 mg/m^2, Cycle 1 /Day 2
|
4870 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 63
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
200 mg/m^2, Cycle 1 /Day 16
|
5360 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 40
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
200 mg/m^2, Cycle 2 /Day 2
|
5290 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 40
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
250 mg/m^2, Cycle 1 /Day 2
|
7990 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 25
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
250 mg/m^2, Cycle 1 /Day 16
|
7990 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 6
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
250 mg/m^2, Cycle 2 /Day 2
|
5290 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 35
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
200 mg (flat dose), Cycle 1 /Day 2
|
3440 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 65
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
200 mg (flat dose), Cycle 1 /Day 16
|
3470 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 61
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
200 mg (flat dose), Cycle 2 /Day 2
|
3640 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 45
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
230 mg (flat dose), Cycle 1 /Day 2
|
4820 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 72
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
230 mg (flat dose), Cycle 1 /Day 16
|
4980 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 35
|
—
|
|
Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618
230 mg (flat dose), Cycle 2 /Day 2
|
3830 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 26
|
—
|
SECONDARY outcome
Timeframe: Phase 2: LY2603618 - Predose and 0, 1, 3, and 24 hours after the end of infusion on Days 2 and 16 of Cycle 1. Gemcitabine - Predose and 0, 10, 60, and 120 minutes after the end of infusion on Days 1 and 15 of Cycle 1.Population: Phase 2 participants who received at least 1 dose of study drug (LY2603618) and had sufficient LY2603618 plasma concentration data to enable determination of the LY2603618 Cmax.
Plasma samples for PK analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine and dFdU plasma concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only the LY2603618 plasma Cmax values are reported at the 230 mg LY2603618 dose level on Cycle 1 /Day 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each time point.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=62 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 2: Maximum Plasma Concentration (Cmax) of Gemcitabine, dFdU, and LY2603618
Cycle 1 /Day 2
|
3170 ng/mL
Geometric Coefficient of Variation 50
|
—
|
|
Phase 2: Maximum Plasma Concentration (Cmax) of Gemcitabine, dFdU, and LY2603618
Cycle 1 /Day 16
|
3410 ng/mL
Geometric Coefficient of Variation 50
|
—
|
|
Phase 2: Maximum Plasma Concentration (Cmax) of Gemcitabine, dFdU, and LY2603618
Cycle 2 /Day 2
|
2390 ng/mL
Geometric Coefficient of Variation 54
|
—
|
SECONDARY outcome
Timeframe: Phase 1: LY2603618 - Predose and 0, 1, 3, 6, 24, 48, and 72 hours after the end of infusion on C1 /D2, C1 /D16, and C2 /D2. Gemcitabine - Predose and 0, 10, 30, 60, and 120 minutes after the end of infusion on C1 /D1, C1 /D15, and C2 /D1.Population: Phase 1 participants who received at least 1 dose of study drug (LY2603618) and had sufficient LY2603618 plasma concentration data to enable calculation of the LY2603618 AUC.
Plasma samples for PK analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine plasma and dFdU concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only LY2603618 plasma AUC from time zero to 24 hours (AUC\[0-24\]), AUC from time zero to the last time point with a measurable concentration (AUC\[0-tlast\]), and AUC from time zero to infinity (AUC\[0-inf\]) values are reported for each LY2603618 dose level on Cycle 1 /Day 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each dose level and time point.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=50 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 70 mg/m^2, Cycle 1 /Day 2
|
21300 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 24
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 70 mg/m^2, Cycle 1 /Day 16
|
21200 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 27
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 70 mg/m^2, Cycle 2 /Day 2
|
19900 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 24
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 105 mg/m^2, Cycle 1 /Day 2
|
40500 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 23
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 105 mg/m^2, Cycle 1 /Day 16
|
50100 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 32
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 105 mg/m^2, Cycle 2 /Day 2
|
49800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 4
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 150 mg/m^2, Cycle 1 /Day 2
|
32200 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 27
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 150 mg/m^2, Cycle 1 /Day 16
|
40000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 29
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 150 mg/m^2, Cycle 2 /Day 2
|
31000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 42
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 200 mg/m^2, Cycle 1 /Day 2
|
40200 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 42
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 200 mg/m^2, Cycle 1 /Day 16
|
39800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 36
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 200 mg/m^2, Cycle 2 /Day 2
|
44300 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 39
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 250 mg/m^2, Cycle 1 /Day 2
|
88800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 27
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 250 mg/m^2, Cycle 1 /Day 16
|
61000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 63
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 250 mg/m^2, Cycle 2 /Day 2
|
40000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 112
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 200 mg (flat), Cycle 1 /Day 2
|
22900 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 77
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 200 mg (flat), Cycle 1 /Day 16
|
28700 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 63
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 200 mg (flat), Cycle 2 /Day 2
|
23800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 62
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 230 mg (flat), Cycle 1 /Day 2
|
32400 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 38
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 230 mg (flat), Cycle 1 /Day 16
|
32300 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 22
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), 230 mg (flat), Cycle 2 /Day 2
|
32500 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 24
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 70 mg/m^2, Cycle 1 /Day 2
|
24600 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 28
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 70 mg/m^2, Cycle 1 /Day 16
|
27500 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 21
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 70 mg/m^2, Cycle 2 /Day 2
|
25800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 29
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 105 mg/m^2, Cycle 1 /Day 2
|
65800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 53
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 105 mg/m^2, Cycle 1 /Day 16
|
75500 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 46
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 105 mg/m^2, Cycle 2 /Day 2
|
79600 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 19
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 150 mg/m^2, Cycle 1 /Day 2
|
41600 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 31
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 150 mg/m^2, Cycle 1 /Day 16
|
52000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 38
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 150 mg/m^2, Cycle 2 /Day 2
|
39800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 45
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 200 mg/m^2, Cycle 1 /Day 2
|
44300 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 85
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 200 mg/m^2, Cycle 1 /Day 16
|
55300 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 51
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 200 mg/m^2, Cycle 2 /Day 2
|
55600 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 51
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 250 mg/m^2, Cycle 1 /Day 2
|
140000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 37
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 250 mg/m^2, Cycle 1 /Day 16
|
98200 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 139
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 250 mg/m^2, Cycle 2 /Day 2
|
60400 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 178
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 200 mg (flat), Cycle 1 /Day 2
|
33100 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 101
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 200 mg (flat), Cycle 1 /Day 16
|
42600 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 88
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 200 mg (flat), Cycle 2 /Day 2
|
32400 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 85
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 230 mg (flat), Cycle 1 /Day 2
|
43000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 50
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 230 mg (flat), Cycle 1 /Day 16
|
51900 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 50
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), 230 mg (flat), Cycle 2 /Day 2
|
45900 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 26
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 70 mg/m^2, Cycle 1 /Day 2
|
24900 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 29
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 70 mg/m^2, Cycle 1 /Day 16
|
28600 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 19
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 70 mg/m^2, Cycle 2 /Day 2
|
27100 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 31
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 105 mg/m^2, Cycle 1 /Day 2
|
78600 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 68
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 105 mg/m^2, Cycle 1 /Day 16
|
79800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 51
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 105 mg/m^2, Cycle 2 /Day 2
|
88800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 25
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 150 mg/m^2, Cycle 1 /Day 2
|
42800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 33
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 150 mg/m^2, Cycle 1 /Day 16
|
54600 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 43
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 150 mg/m^2, Cycle 2 /Day 2
|
41000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 46
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 200 mg/m^2, Cycle 1 /Day 2
|
60300 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 58
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 200 mg/m^2, Cycle 1 /Day 16
|
56800 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 54
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 200 mg/m^2, Cycle 2 /Day 2
|
65400 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 49
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 250 mg/m^2, Cycle 1 /Day 2
|
153000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 41
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 250 mg/m^2, Cycle 1 /Day 16
|
101000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 141
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 250 mg/m^2, Cycle 2 /Day 2
|
70500 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 216
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 200 mg (flat), Cycle 1 /Day 2
|
35200 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 117
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 200 mg (flat), Cycle 1 /Day 16
|
45700 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 93
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 200 mg (flat), Cycle 2 /Day 2
|
34400 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 93
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 230 mg (flat), Cycle 1 /Day 2
|
45200 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 50
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 230 mg (flat), Cycle 1 /Day 16
|
57700 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 58
|
—
|
|
Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), 230 mg (flat), Cycle 2 /Day 2
|
48000 nanogram*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 26
|
—
|
SECONDARY outcome
Timeframe: Phase 2: LY2603618 - Predose and 0, 1, 3, and 24 hours after the end of infusion on Days 2 and 16 of Cycle 1. Gemcitabine - Predose and 0, 10, 60, and 120 minutes after the end of infusion on Days 1 and 15 of Cycle 1.Population: Phase 2 participants who received at least 1 dose of study drug (LY2603618) and had sufficient LY2603618 plasma concentration data to enable calculation of the LY2603618 AUC.
Plasma samples for PK analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine and dFdU plasma concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only the LY2603618 plasma AUC(0-24), AUC(0-tlast), and AUC(0-inf) values are reported for the 230 mg LY2603618 dose on Cycle 1 /Day 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each time point.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=62 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), Cycle 1 /Day 2
|
23200 ng*h/mL
Geometric Coefficient of Variation 68
|
—
|
|
Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), Cycle 1 /Day 16
|
23700 ng*h/mL
Geometric Coefficient of Variation 60
|
—
|
|
Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-24), Cycle 2 /Day 2
|
19800 ng*h/mL
Geometric Coefficient of Variation 63
|
—
|
|
Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), Cycle 1 /Day 2
|
22200 ng*h/mL
Geometric Coefficient of Variation 73
|
—
|
|
Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), Cycle 1 /Day 16
|
20800 ng*h/mL
Geometric Coefficient of Variation 78
|
—
|
|
Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-tlast), Cycle 2 /Day 2
|
20100 ng*h/mL
Geometric Coefficient of Variation 64
|
—
|
|
Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), Cycle 1 /Day 2
|
29400 ng*h/mL
Geometric Coefficient of Variation 84
|
—
|
|
Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), Cycle 1 /Day 16
|
29100 ng*h/mL
Geometric Coefficient of Variation 74
|
—
|
|
Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618
AUC(0-inf), Cycle 2 /Day 2
|
23300 ng*h/mL
Geometric Coefficient of Variation 69
|
—
|
SECONDARY outcome
Timeframe: Phase 2: Baseline to measured progressive disease or date of death from any causePopulation: Phase 2 participants who were randomized.
Progression-free survival (PFS) time was defined as the time from the date of randomization to the first date of progressive disease (symptomatic or objective) or death due to any cause, whichever occurred first. For participants who were not known to have died or progressed as of the data-inclusion cutoff date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS was summarized using Kaplan-Meier estimates.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=65 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
n=34 Participants
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 2: Progression-free Survival (PFS)
|
3.5 months
Interval 2.1 to 3.6
|
5.6 months
Interval 2.6 to 7.6
|
SECONDARY outcome
Timeframe: Phase 2: Baseline to measured progressive disease or date of death from any causePopulation: Phase 2 participants who were randomized.
Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=65 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
n=34 Participants
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 2: Overall Response Rate
|
21.5 percentage of participants
Interval 12.3 to 33.5
|
8.8 percentage of participants
Interval 1.9 to 23.7
|
SECONDARY outcome
Timeframe: Phase 2: Baseline to measured progressive disease or date of death from any causePopulation: Phase 2 participants who were randomized.
Clinical benefit rate is the best response CR, PR, or stable disease (SD) as classified by the investigators according to the RECIST v1.1 guidelines. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Overall response rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=65 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
n=34 Participants
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 2: Clinical Benefit Rate
|
55.4 percentage of participants
Interval 42.5 to 67.7
|
64.7 percentage of participants
Interval 46.5 to 80.3
|
SECONDARY outcome
Timeframe: Phase 2. Baseline to measured progressive disease or date of death from any causePopulation: Phase 2 participants who received at least 1 dose of study drug and had a confirmed response (CR or PR).
Duration of response was defined as the time from the first observation of complete response (CR) or partial response (PR) to the first observation of progressive disease or death from any cause. For participants who were not known to have died as of the data-inclusion cut-off date and who do not have progressive disease, the duration was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent anticancer therapy (systemic, radiologic, or surgery). Participants were also censored at the last valid assessment prior to missing more than 1 consecutive scheduled assessment. Duration of response was summarized using Kaplan-Meier estimates.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=14 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
n=3 Participants
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 2: Duration of Response
|
3.5 months
Interval 1.9 to 5.8
|
6.0 months
Interval 3.7 to 6.8
|
SECONDARY outcome
Timeframe: Phase 1: Days 2 and 16 of Cycle 1Population: Phase 1 participants who received at least 1 dose of LY2603618 and had evaluable ECG data.
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Twelve-lead electrocardiogram (ECG) data was used to calculate the corrected QT (QTc) based on Fridericia's formula (QTc=QT/RR\^0.33, where RR is the interval between two R waves). For each participant, changes in QTc were calculated by subtracting the reading taken before LY2603618 administration from the reading taken after LY2603618 administration on Days 2 and 16 during Cycle 1. The number of participants in which the change in QTc was \<=30 milliseconds (msec), \>30-60 msec, or \>60 msec is presented by dose group and overall.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=49 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 1: Electrocardiogram QTc Prolongation
70 mg/m^2, <=30 msec
|
2 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
70 mg/m^2, >30-60 msec
|
1 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
70 mg/m^2, >60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
105 mg/m^2, <=30 msec
|
2 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
105 mg/m^2, >30-60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
105 mg/m^2, >60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
150 mg/m^2, <=30 msec
|
6 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
150 mg/m^2, >30-60 msec
|
1 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
150 mg/m^2, >60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
200 mg/m^2, <=30 msec
|
11 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
200 mg/m^2, >30-60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
200 mg/m^2, >60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
250 mg/m^2, <=30 msec
|
6 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
250 mg/m^2, >30-60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
250 mg/m^2, >60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
200 mg (flat dose), <=30 msec
|
9 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
200 mg (flat dose), >30-60 msec
|
1 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
200 mg (flat dose), >60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
230 mg (flat dose), <=30 msec
|
8 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
230 mg (flat dose), >30-60 msec
|
2 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
230 mg (flat dose), >60 msec
|
0 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
Total, <=30 msec
|
44 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
Total, >30-60 msec
|
5 Participants
|
—
|
|
Phase 1: Electrocardiogram QTc Prolongation
Total, >60 msec
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Phase 2: Days 2 and 16 of Cycle 1Population: Phase 2 participants who received at least 1 dose of LY2603618 and had evaluable ECG data.
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Twelve-lead ECG data was used to calculate QTc based on Fridericia's formula (QTc=QT/RR\^0.33, where RR is the interval between two R waves). For each participant, changes in QTc were calculated by subtracting the reading taken before LY2603618 administration from the reading taken after LY2603618 administration on Days 2 and 16 during Cycle 1. The number of participants in which the change in QTc was \<=30 milliseconds (msec), \>30-60 msec, or \>60 msec is presented.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=60 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Phase 2: Electrocardiogram QTc Prolongation
<=30 msec
|
55 Participants
|
—
|
|
Phase 2: Electrocardiogram QTc Prolongation
>30-60 msec
|
5 Participants
|
—
|
|
Phase 2: Electrocardiogram QTc Prolongation
>60 msec
|
0 Participants
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Phase 1: Time of last dose of study drug through the end of the follow-up periodPopulation: Participants enrolled in Phase 1.
The number of participants who died during the post-study period of Phase 1 does not include the outcomes for the 4 participants who died while on treatment during Phase 2 as captured in the Participant Flow Table. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=50 Participants
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70-250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|
|
Number of Deaths During the Phase 1 Post-study Period
Total deaths
|
5 Participants
|
—
|
|
Number of Deaths During the Phase 1 Post-study Period
Deaths within 30 days of last dose of study drug
|
4 Participants
|
—
|
|
Number of Deaths During the Phase 1 Post-study Period
Deaths during the follow-up period
|
1 Participants
|
—
|
Adverse Events
Phase 1: LY2603618 + Gemcitabine
Serious events: 21 serious events
Other events: 48 other events
Deaths: 0 deaths
Phase 2: LY2603618 + Gemcitabine
Serious events: 27 serious events
Other events: 64 other events
Deaths: 0 deaths
Phase 2: Gemcitabine
Serious events: 18 serious events
Other events: 34 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=50 participants at risk
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70 to 250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: LY2603618 + Gemcitabine
n=65 participants at risk
LY2603618: 230 mg flat dose LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
Gemcitabine: Participants were administered 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
n=34 participants at risk
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
2.9%
1/34 • Number of events 1
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Blood and lymphatic system disorders
Haemolytic uraemic syndrome
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Blood and lymphatic system disorders
Haemorrhagic anaemia
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Blood and lymphatic system disorders
Neutropenia
|
4.0%
2/50 • Number of events 2
|
0.00%
0/65
|
0.00%
0/34
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.0%
3/50 • Number of events 3
|
0.00%
0/65
|
0.00%
0/34
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/50
|
3.1%
2/65 • Number of events 2
|
0.00%
0/34
|
|
Cardiac disorders
Bundle branch block left
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/50
|
3.1%
2/65 • Number of events 2
|
0.00%
0/34
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/50
|
3.1%
2/65 • Number of events 2
|
5.9%
2/34 • Number of events 2
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Gastrointestinal disorders
Constipation
|
2.0%
1/50 • Number of events 1
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Gastrointestinal disorders
Diarrhoea
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Gastrointestinal disorders
Duodenal ulcer perforation
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Gastrointestinal disorders
Intestinal obstruction
|
4.0%
2/50 • Number of events 2
|
0.00%
0/65
|
0.00%
0/34
|
|
Gastrointestinal disorders
Nausea
|
4.0%
2/50 • Number of events 2
|
1.5%
1/65 • Number of events 1
|
2.9%
1/34 • Number of events 1
|
|
Gastrointestinal disorders
Pancreatic pseudocyst
|
0.00%
0/50
|
1.5%
1/65 • Number of events 2
|
0.00%
0/34
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Gastrointestinal disorders
Pancreatitis acute
|
2.0%
1/50 • Number of events 2
|
0.00%
0/65
|
0.00%
0/34
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Gastrointestinal disorders
Vomiting
|
6.0%
3/50 • Number of events 3
|
1.5%
1/65 • Number of events 1
|
2.9%
1/34 • Number of events 2
|
|
General disorders
Device occlusion
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
General disorders
Fatigue
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
General disorders
Pyrexia
|
2.0%
1/50 • Number of events 1
|
4.6%
3/65 • Number of events 3
|
5.9%
2/34 • Number of events 2
|
|
General disorders
Thrombosis in device
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 2
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/50
|
4.6%
3/65 • Number of events 3
|
2.9%
1/34 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Infections and infestations
Abdominal sepsis
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Infections and infestations
Bacteraemia
|
2.0%
1/50 • Number of events 1
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Infections and infestations
Bacterial sepsis
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Infections and infestations
Bronchitis
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Infections and infestations
Cellulitis
|
4.0%
2/50 • Number of events 2
|
0.00%
0/65
|
0.00%
0/34
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Infections and infestations
Device related infection
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Infections and infestations
Pneumonia
|
0.00%
0/50
|
3.1%
2/65 • Number of events 2
|
0.00%
0/34
|
|
Infections and infestations
Renal abscess
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Infections and infestations
Sepsis
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/50
|
0.00%
0/65
|
8.8%
3/34 • Number of events 3
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Investigations
C-reactive protein increased
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Investigations
International normalised ratio increased
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
8.8%
3/34 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
2.9%
1/34 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/50
|
3.1%
2/65 • Number of events 2
|
0.00%
0/34
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant ascites
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to ovary
|
0.00%
0/24
|
0.00%
0/23
|
7.1%
1/14 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Nervous system disorders
Syncope
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Renal and urinary disorders
Nephrotic syndrome
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/50
|
0.00%
0/65
|
5.9%
2/34 • Number of events 3
|
|
Renal and urinary disorders
Ureteric stenosis
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/50
|
3.1%
2/65 • Number of events 2
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
2.9%
1/34 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Vascular disorders
Deep vein thrombosis
|
4.0%
2/50 • Number of events 2
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Vascular disorders
Hypotension
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Vascular disorders
Phlebitis
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Vascular disorders
Phlebitis superficial
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
0.00%
0/34
|
|
Vascular disorders
Venous thrombosis limb
|
0.00%
0/50
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
Other adverse events
| Measure |
Phase 1: LY2603618 + Gemcitabine
n=50 participants at risk
All participants in Phase 1 received LY2603618 in combination with gemcitabine.
LY2603618: 70 to 250 mg/m\^2 LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received LY2603618 as part of the dose escalation cohort of Phase 1 (dose of 70, 105, 150, 200, or 250 mg/m\^2) or as part of the expansion cohort of Phase 1 (flat dose of 200 or 230 mg). The flat dose cohorts were conducted in parallel.
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: LY2603618 + Gemcitabine
n=65 participants at risk
LY2603618: 230 mg flat dose LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
Gemcitabine: Participants were administered 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression. Participants received gemcitabine 24 hours prior to LY2603618 administration.
|
Phase 2: Gemcitabine
n=34 participants at risk
Gemcitabine: 1000 mg/m\^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.
|
|---|---|---|---|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.0%
4/50 • Number of events 4
|
1.5%
1/65 • Number of events 1
|
14.7%
5/34 • Number of events 6
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.0%
3/50 • Number of events 4
|
9.2%
6/65 • Number of events 7
|
14.7%
5/34 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
8.0%
4/50 • Number of events 8
|
0.00%
0/65
|
0.00%
0/34
|
|
Metabolism and nutrition disorders
Vitamin d deficiency
|
6.0%
3/50 • Number of events 3
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.0%
3/50 • Number of events 3
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.0%
6/50 • Number of events 6
|
13.8%
9/65 • Number of events 10
|
11.8%
4/34 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
14.0%
7/50 • Number of events 9
|
3.1%
2/65 • Number of events 2
|
5.9%
2/34 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
6.0%
3/50 • Number of events 3
|
0.00%
0/65
|
5.9%
2/34 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.0%
5/50 • Number of events 7
|
12.3%
8/65 • Number of events 9
|
2.9%
1/34 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/50
|
0.00%
0/65
|
5.9%
2/34 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
10.0%
5/50 • Number of events 5
|
7.7%
5/65 • Number of events 5
|
11.8%
4/34 • Number of events 4
|
|
Nervous system disorders
Dysgeusia
|
6.0%
3/50 • Number of events 5
|
7.7%
5/65 • Number of events 5
|
5.9%
2/34 • Number of events 2
|
|
Nervous system disorders
Headache
|
10.0%
5/50 • Number of events 7
|
10.8%
7/65 • Number of events 10
|
5.9%
2/34 • Number of events 2
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
8.0%
4/50 • Number of events 4
|
10.8%
7/65 • Number of events 8
|
5.9%
2/34 • Number of events 4
|
|
Psychiatric disorders
Anxiety
|
8.0%
4/50 • Number of events 4
|
0.00%
0/65
|
8.8%
3/34 • Number of events 3
|
|
Psychiatric disorders
Confusional state
|
2.0%
1/50 • Number of events 1
|
1.5%
1/65 • Number of events 1
|
5.9%
2/34 • Number of events 2
|
|
Psychiatric disorders
Depression
|
12.0%
6/50 • Number of events 7
|
3.1%
2/65 • Number of events 2
|
8.8%
3/34 • Number of events 4
|
|
Psychiatric disorders
Insomnia
|
14.0%
7/50 • Number of events 9
|
6.2%
4/65 • Number of events 4
|
17.6%
6/34 • Number of events 8
|
|
Renal and urinary disorders
Pollakiuria
|
6.0%
3/50 • Number of events 3
|
0.00%
0/65
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
10/50 • Number of events 12
|
10.8%
7/65 • Number of events 7
|
14.7%
5/34 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/50
|
3.1%
2/65 • Number of events 2
|
5.9%
2/34 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.0%
8/50 • Number of events 11
|
18.5%
12/65 • Number of events 13
|
5.9%
2/34 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
8.0%
4/50 • Number of events 7
|
3.1%
2/65 • Number of events 2
|
2.9%
1/34 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
10.0%
5/50 • Number of events 5
|
1.5%
1/65 • Number of events 2
|
0.00%
0/34
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
4.0%
2/50 • Number of events 2
|
10.8%
7/65 • Number of events 8
|
14.7%
5/34 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
2.0%
1/50 • Number of events 1
|
6.2%
4/65 • Number of events 4
|
0.00%
0/34
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
8.0%
4/50 • Number of events 5
|
3.1%
2/65 • Number of events 2
|
0.00%
0/34
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.0%
3/50 • Number of events 3
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.0%
1/50 • Number of events 1
|
6.2%
4/65 • Number of events 6
|
5.9%
2/34 • Number of events 2
|
|
Vascular disorders
Deep vein thrombosis
|
2.0%
1/50 • Number of events 1
|
6.2%
4/65 • Number of events 4
|
8.8%
3/34 • Number of events 3
|
|
Vascular disorders
Flushing
|
12.0%
6/50 • Number of events 8
|
0.00%
0/65
|
0.00%
0/34
|
|
Vascular disorders
Hypertension
|
2.0%
1/50 • Number of events 1
|
4.6%
3/65 • Number of events 3
|
8.8%
3/34 • Number of events 3
|
|
Vascular disorders
Hypotension
|
10.0%
5/50 • Number of events 5
|
4.6%
3/65 • Number of events 3
|
14.7%
5/34 • Number of events 5
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.00%
0/50
|
6.2%
4/65 • Number of events 4
|
0.00%
0/34
|
|
Blood and lymphatic system disorders
Anaemia
|
46.0%
23/50 • Number of events 29
|
24.6%
16/65 • Number of events 21
|
29.4%
10/34 • Number of events 13
|
|
Blood and lymphatic system disorders
Leukocytosis
|
6.0%
3/50 • Number of events 3
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Blood and lymphatic system disorders
Leukopenia
|
8.0%
4/50 • Number of events 5
|
12.3%
8/65 • Number of events 27
|
17.6%
6/34 • Number of events 10
|
|
Blood and lymphatic system disorders
Lymphopenia
|
10.0%
5/50 • Number of events 6
|
6.2%
4/65 • Number of events 7
|
11.8%
4/34 • Number of events 4
|
|
Blood and lymphatic system disorders
Neutropenia
|
32.0%
16/50 • Number of events 26
|
23.1%
15/65 • Number of events 49
|
29.4%
10/34 • Number of events 24
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
46.0%
23/50 • Number of events 46
|
35.4%
23/65 • Number of events 63
|
44.1%
15/34 • Number of events 39
|
|
Blood and lymphatic system disorders
Thrombocytosis
|
2.0%
1/50 • Number of events 1
|
0.00%
0/65
|
5.9%
2/34 • Number of events 5
|
|
Cardiac disorders
Sinus tachycardia
|
6.0%
3/50 • Number of events 3
|
0.00%
0/65
|
2.9%
1/34 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.0%
3/50 • Number of events 3
|
1.5%
1/65 • Number of events 2
|
0.00%
0/34
|
|
Gastrointestinal disorders
Abdominal distension
|
8.0%
4/50 • Number of events 4
|
3.1%
2/65 • Number of events 3
|
5.9%
2/34 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain
|
24.0%
12/50 • Number of events 12
|
21.5%
14/65 • Number of events 19
|
14.7%
5/34 • Number of events 7
|
|
Gastrointestinal disorders
Abdominal pain upper
|
4.0%
2/50 • Number of events 2
|
7.7%
5/65 • Number of events 5
|
2.9%
1/34 • Number of events 1
|
|
Gastrointestinal disorders
Anorectal discomfort
|
0.00%
0/50
|
0.00%
0/65
|
5.9%
2/34 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
34.0%
17/50 • Number of events 22
|
32.3%
21/65 • Number of events 27
|
26.5%
9/34 • Number of events 10
|
|
Gastrointestinal disorders
Diarrhoea
|
16.0%
8/50 • Number of events 10
|
32.3%
21/65 • Number of events 36
|
29.4%
10/34 • Number of events 15
|
|
Gastrointestinal disorders
Dyspepsia
|
6.0%
3/50 • Number of events 3
|
6.2%
4/65 • Number of events 4
|
2.9%
1/34 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
2.0%
1/50 • Number of events 1
|
6.2%
4/65 • Number of events 7
|
0.00%
0/34
|
|
Gastrointestinal disorders
Gastritis
|
6.0%
3/50 • Number of events 3
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Gastrointestinal disorders
Haemorrhoids
|
4.0%
2/50 • Number of events 2
|
0.00%
0/65
|
5.9%
2/34 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
40.0%
20/50 • Number of events 25
|
41.5%
27/65 • Number of events 42
|
44.1%
15/34 • Number of events 21
|
|
Gastrointestinal disorders
Steatorrhoea
|
0.00%
0/50
|
1.5%
1/65 • Number of events 1
|
5.9%
2/34 • Number of events 2
|
|
Gastrointestinal disorders
Stomatitis
|
10.0%
5/50 • Number of events 9
|
20.0%
13/65 • Number of events 14
|
5.9%
2/34 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
28.0%
14/50 • Number of events 16
|
29.2%
19/65 • Number of events 35
|
11.8%
4/34 • Number of events 5
|
|
General disorders
Asthenia
|
8.0%
4/50 • Number of events 5
|
15.4%
10/65 • Number of events 19
|
14.7%
5/34 • Number of events 8
|
|
General disorders
Chills
|
10.0%
5/50 • Number of events 6
|
13.8%
9/65 • Number of events 15
|
5.9%
2/34 • Number of events 2
|
|
General disorders
Fatigue
|
62.0%
31/50 • Number of events 50
|
33.8%
22/65 • Number of events 28
|
41.2%
14/34 • Number of events 19
|
|
General disorders
Influenza like illness
|
6.0%
3/50 • Number of events 3
|
4.6%
3/65 • Number of events 8
|
8.8%
3/34 • Number of events 3
|
|
General disorders
Infusion site pain
|
10.0%
5/50 • Number of events 10
|
0.00%
0/65
|
2.9%
1/34 • Number of events 4
|
|
General disorders
Irritability
|
6.0%
3/50 • Number of events 3
|
0.00%
0/65
|
0.00%
0/34
|
|
General disorders
Non-cardiac chest pain
|
6.0%
3/50 • Number of events 3
|
1.5%
1/65 • Number of events 1
|
2.9%
1/34 • Number of events 1
|
|
General disorders
Oedema peripheral
|
16.0%
8/50 • Number of events 9
|
29.2%
19/65 • Number of events 23
|
35.3%
12/34 • Number of events 16
|
|
General disorders
Pyrexia
|
30.0%
15/50 • Number of events 33
|
29.2%
19/65 • Number of events 23
|
32.4%
11/34 • Number of events 14
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
4.0%
2/50 • Number of events 2
|
3.1%
2/65 • Number of events 2
|
11.8%
4/34 • Number of events 4
|
|
Immune system disorders
Drug hypersensitivity
|
10.0%
5/50 • Number of events 5
|
3.1%
2/65 • Number of events 5
|
0.00%
0/34
|
|
Infections and infestations
Oral candidiasis
|
8.0%
4/50 • Number of events 4
|
1.5%
1/65 • Number of events 2
|
2.9%
1/34 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
6.0%
3/50 • Number of events 4
|
0.00%
0/65
|
0.00%
0/34
|
|
Infections and infestations
Urinary tract infection
|
6.0%
3/50 • Number of events 3
|
3.1%
2/65 • Number of events 2
|
8.8%
3/34 • Number of events 3
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
6.0%
3/50 • Number of events 3
|
1.5%
1/65 • Number of events 1
|
0.00%
0/34
|
|
Injury, poisoning and procedural complications
Procedural pain
|
6.0%
3/50 • Number of events 4
|
0.00%
0/65
|
0.00%
0/34
|
|
Investigations
Alanine aminotransferase increased
|
20.0%
10/50 • Number of events 15
|
20.0%
13/65 • Number of events 18
|
17.6%
6/34 • Number of events 6
|
|
Investigations
Aspartate aminotransferase increased
|
22.0%
11/50 • Number of events 14
|
15.4%
10/65 • Number of events 15
|
14.7%
5/34 • Number of events 5
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/50
|
7.7%
5/65 • Number of events 5
|
8.8%
3/34 • Number of events 3
|
|
Investigations
Blood lactate dehydrogenase increased
|
2.0%
1/50 • Number of events 1
|
3.1%
2/65 • Number of events 2
|
8.8%
3/34 • Number of events 3
|
|
Investigations
Gamma-glutamyltransferase increased
|
8.0%
4/50 • Number of events 4
|
18.5%
12/65 • Number of events 12
|
8.8%
3/34 • Number of events 3
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/50
|
3.1%
2/65 • Number of events 2
|
5.9%
2/34 • Number of events 3
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/50
|
4.6%
3/65 • Number of events 3
|
5.9%
2/34 • Number of events 6
|
|
Investigations
Platelet count decreased
|
0.00%
0/50
|
10.8%
7/65 • Number of events 11
|
2.9%
1/34 • Number of events 5
|
|
Investigations
Weight decreased
|
4.0%
2/50 • Number of events 3
|
10.8%
7/65 • Number of events 8
|
8.8%
3/34 • Number of events 3
|
|
Investigations
White blood cell count decreased
|
4.0%
2/50 • Number of events 2
|
3.1%
2/65 • Number of events 4
|
5.9%
2/34 • Number of events 8
|
|
Metabolism and nutrition disorders
Decreased appetite
|
32.0%
16/50 • Number of events 19
|
32.3%
21/65 • Number of events 22
|
14.7%
5/34 • Number of events 6
|
|
Metabolism and nutrition disorders
Dehydration
|
6.0%
3/50 • Number of events 4
|
1.5%
1/65 • Number of events 1
|
8.8%
3/34 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.0%
3/50 • Number of events 8
|
18.5%
12/65 • Number of events 13
|
11.8%
4/34 • Number of events 6
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/50
|
3.1%
2/65 • Number of events 2
|
8.8%
3/34 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
2.0%
1/50 • Number of events 2
|
6.2%
4/65 • Number of events 4
|
8.8%
3/34 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
2.0%
1/50 • Number of events 1
|
3.1%
2/65 • Number of events 4
|
17.6%
6/34 • Number of events 6
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60