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A Study of LY2157299 in Participants With Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT01246986
Recruitment Status : Completed
First Posted : November 24, 2010
Results First Posted : August 7, 2020
Last Update Posted : January 12, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Hepatocellular
Interventions Drug: LY2157299
Drug: Sorafenib
Drug: Ramucirumab
Enrollment 204
Recruitment Details  
Pre-assignment Details Participants who had progressive disease or death are defined as completed. Per the protocol, following an interim analysis, the decision was taken to no longer randomize participants to the 160 mg LY2157299 arm.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
Hide Arm/Group Description 80 mg LY2157299 given orally twice daily (BID) for 14 days followed by 14 days off (28-day cycle). 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). 80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). 150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). 80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle). 150 mg LY2157299 given twice orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle).
Period Title: Overall Study
Started 37 72 40 3 44 3 5
Received at Least 1 Dose of Study Drug 37 72 40 3 44 3 5
Completed 34 67 34 3 40 2 5
Not Completed 3 5 6 0 4 1 0
Reason Not Completed
Lost to Follow-up             0             1             3             0             0             1             0
Withdrawal by Subject             3             4             3             0             4             0             0
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab Total
Hide Arm/Group Description 80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).. 150mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). 80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). 150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). 80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle). 150 mg LY2157299 given twice BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle). Total of all reporting groups
Overall Number of Baseline Participants 37 72 40 3 44 3 5 204
Hide Baseline Analysis Population Description
All enrolled participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants 72 participants 40 participants 3 participants 44 participants 3 participants 5 participants 204 participants
63.4  (10.8) 63.3  (10.8) 68.1  (9.6) 70.3  (4.7) 63.7  (9.8) 54.0  (11.3) 63.2  (11.2) 64.3  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 72 participants 40 participants 3 participants 44 participants 3 participants 5 participants 204 participants
Female 5 13 4 0 5 0 0 27
Male 32 59 36 3 39 3 5 177
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 72 participants 40 participants 3 participants 44 participants 3 participants 5 participants 204 participants
American Indian or Alaska Native 0 0 0 1 0 0 0 1
Asian 1 7 1 0 6 2 4 21
Native Hawaiian or Other Pacific Islander 0 2 0 0 7 0 0 9
Black or African American 2 3 1 0 2 0 1 9
White 34 58 35 2 20 0 0 149
More than one race 0 0 0 0 0 0 0 0
Unknown or Not Reported 0 2 3 0 9 1 0 15
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 72 participants 40 participants 3 participants 44 participants 3 participants 5 participants 204 participants
New Zealand 2 5 4 0 12 0 0 23
United States 6 12 4 1 10 3 5 41
Italy 12 15 9 0 4 0 0 40
Australia 0 3 2 0 0 0 0 5
France 12 27 16 0 14 0 0 69
Germany 4 7 4 2 4 0 0 21
Spain 1 3 1 0 0 0 0 5
Alpha-Fetoprotein  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants 72 participants 40 participants 3 participants 44 participants 3 participants 5 participants 204 participants
< 200 nanograms per Liter (µg/L) 9 23 28 2 20 1 2 85
200 - 400 (µg/L) 3 5 0 0 4 0 0 12
> 400 (µg/L) 23 43 0 1 16 2 2 87
Unknown/Not reported 2 1 12 0 4 0 1 20
1.Primary Outcome
Title Change From Baseline in Relationship of Biomarker Alpha-fetoprotein (AFP) to Overall Survival (OS)
Hide Description Biomarker response was defined as a > 20% decrease in the biomarker AFP from baseline during 8 weeks of treatment. Data presented is median overall survival of those participants who achieved the defined biomarker response. Participants enrolled in Part A had a baseline AFP level of >1.5 upper limit normal (ULN). Participants enrolled in Part B had baseline AFP level <1.5 ULN.
Time Frame Baseline, discontinuation from any cause (Up to 83 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug, achieved a >20% reduction in biomarker AFP, and had evaluable post-baseline biomarker data. Due to low enrollment into Part C Cohort - 160 mg reporting group, Kaplan Meier analysis for OS was not conducted in this subgroup. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B LY2157299 Part C LY2157299
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle) for Cohort 1.
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
Overall Number of Participants Analyzed 8 14 10 27
Median (95% Confidence Interval)
Unit of Measure: Months
19.0
(1.5 to 25.1)
21.5
(2.9 to 34.2)
24.2 [1] 
(3.0 to NA)
17.9
(12.6 to 32.8)
[1]
Part B 95% Confidence Interval (CI) upper limit non-estimable
2.Primary Outcome
Title Change From Baseline in Relationship of Biomarker Transforming Growth Factor - Beta (TGF-β) to Overall Survival (OS)
Hide Description Biomarker response was defined as a > 20% decrease in the biomarker TGF-B from baseline. Data presented is median overall survival of those participants who achieved biomarker response.
Time Frame Baseline,discontinuation from any cause (Up to 83 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug, achieved a >20% reduction in biomarker TGF-β and had evaluable post-baseline biomarker data. Due to low enrollment in Part C Cohort 1 - 160 mg reporting group, Kaplan Meier analysis for OS was not conducted in this subgroup. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B LY2157299 Part C LY2157299
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle) for Cohort 1.
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle) for Cohort 2.
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days 0ff (28-day cycle).
Overall Number of Participants Analyzed 16 34 28 31
Median (95% Confidence Interval)
Unit of Measure: Months
11.9
(5.4 to 15.6)
10.1
(4.9 to 15.5)
21.9 [1] 
(12.4 to NA)
22.88
(16.2 to 31.8)
[1]
Part B 95% CI upper limit was non-estimable.
3.Primary Outcome
Title Time to Progression (TTP)
Hide Description TTP is measured from the date of first dose to the first date of progression of disease based on the investigator review of tumor response using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame Randomization to date of first measured progressive disease (Up to 36 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who receive at least one dose of study drug. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib
150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day
Overall Number of Participants Analyzed 37 72 40 3 44
Median (90% Confidence Interval)
Unit of Measure: Weeks
12.1
(6.3 to 17.6)
7.1
(6.3 to 12.7)
18.0
(10.0 to 24.0)
36.0
(18.0 to 36.0)
17.9
(12.1 to 24.0)
4.Secondary Outcome
Title Population Pharmacokinetics (PK) Mean Population Clearance of Galunisertib
Hide Description Population mean (between-subject coefficient variance [CV %]) apparent clearance.
Time Frame Cycle (C) 1: Day (D)1: Predose, 0.5-2 hours(h) Postdose; D14: Predose, 0.5-2, 3-5 h, Postdose; D15 Morning; D22 Morning; Predose C2 and C3 Predose D1
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug, regardless of dose, with evaluable PK data. Per protocol, Part D collected safety data only.
Arm/Group Title LY2157299
Hide Arm/Group Description:
LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
Overall Number of Participants Analyzed 143
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour (L/hr)
33.6
(48%)
5.Secondary Outcome
Title Recommended Dose for Phase 3 Hepatocellular Carcinoma (HCC) Trials
Hide Description [Not Specified]
Time Frame Cycle 1 (28 Days)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Part A and Part B.
Arm/Group Title LY2157299
Hide Arm/Group Description:
LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
Overall Number of Participants Analyzed 74
Measure Type: Number
Unit of Measure: milligrams (mg)
300
6.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS duration is measured from the date of first dose to the date of death from any cause.
Time Frame Randomization to date of death from any cause (Up to 83 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
Overall Number of Participants Analyzed 37 72 40 3 44
Median (90% Confidence Interval)
Unit of Measure: Weeks
39.1
(24.1 to 52.6)
29.6
(19.6 to 38.6)
73.0
(45.4 to 104.7)
30.3
(28.4 to 70.3)
89.6
(70.3 to 104.9)
7.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS duration is measure from the date of first dose to the first date of objective progression of disease or death from any cause. Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame Randomization to measured progressive disease or death from any cause (Up to 45 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day
150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
Overall Number of Participants Analyzed 37 72 40 3 44
Median (90% Confidence Interval)
Unit of Measure: Weeks
12
(6.3 to 12.6)
6.6
(6.1 to 10.9)
13.4
(7.4 to 23.3)
28.4
(6.0 to 36.0)
28.4
(17.4 to 45.3)
8.Secondary Outcome
Title Percentage of Participants Achieving an Objective Response (Response Rate)
Hide Description The percentage of participants who achieved best overall response of either Complete Response (CR) or Partial Response (PR). The overall response rate for each dose with be estimated by dividing the number of confirmed responders by the number of participants who received at least one dose of study drug. Per RECIST v.1.0 criteria CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 millimeter (mm). Tumor-marker results must have normalized. PR is defined as at least 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.
Time Frame Randomization to measured progressive disease (Up to 36 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
Overall Number of Participants Analyzed 30 46 27 3 44
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response 0 0 0 0 0
Partial Response 0 0 3.7 0 2.3
9.Secondary Outcome
Title Duration of Tumor Response (DoR)
Hide Description DoR is measured from the date of the first objective status assessment of a Complete Response (CR) or Partial Response (PR), as determined by RECIST v1.1, to the first date of objective progression of disease or death from any cause. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 millimeter (mm). Tumor-marker results must have normalized. PR is defined as at least 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
Time Frame Time of response to measured progressive disease or death from any cause (Up to 84 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug with assessment of CR or PR. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
80 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle
150 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle
Overall Number of Participants Analyzed 0 0 2 0 4
Median (90% Confidence Interval)
Unit of Measure: Weeks
37.6
(25.1 to 50.1)
40.2
(12.1 to 84.1)
10.Secondary Outcome
Title Time to Treatment Failure (TTF)
Hide Description TTF is measured from the date of first dose until the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause.
Time Frame Randomization to the date of discontinuation of study treatment due to adverse event, progression of disease, or death from any cause (Up to 75 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
80 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
150 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle).
Overall Number of Participants Analyzed 37 72 40 3 44
Median (90% Confidence Interval)
Unit of Measure: Weeks
13.4
(8.6 to 18.0)
9.9
(8.1 to 12.1)
19.3
(12.1 to 26.3)
26.3
(19.3 to 54.0)
49.3
(18.3 to 75.3)
11.Secondary Outcome
Title Change From Baseline in Functional Assessment of Cancer Therapy, Hepatobiliary (FACT-Hep) Sub-scores and Total Score
Hide Description FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72; FACT-Hep score range 1-180, and Trial-Outcome Index (TOI) score range 1-128, to assess health related quality of life in participants with cancer. Higher scores reflect a better health state.
Time Frame Baseline, Day 1 Cycle 4
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with baseline and one post-baseline FACT-Hep Questionnaire in Cycles 2, 3, or 4. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle).
150 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle).
Overall Number of Participants Analyzed 30 51 38 3 39
Mean (Standard Deviation)
Unit of Measure: units on a scale
PWB Number Analyzed 30 participants 51 participants 38 participants 3 participants 39 participants
0.06  (3.6) -0.16  (5.0) 0.04  (3.4) -1.67  (1.5) -1.75  (4.4)
SWB Number Analyzed 30 participants 51 participants 38 participants 3 participants 39 participants
0.96  (2.9) 0.24  (3.4) 0.37  (4.5) -1.11  (2.8) 0.41  (3.6)
EWB Number Analyzed 30 participants 51 participants 38 participants 3 participants 39 participants
0.55  (2.7) 1.17  (3.9) 1.13  (4.1) 2.87  (2.8) 0.85  (2.5)
FWB Number Analyzed 30 participants 51 participants 38 participants 3 participants 39 participants
-0.02  (5.3) 0.84  (3.6) 1.20  (4.7) -1.00  (1.0) -1.19  (4.6)
HCS Number Analyzed 30 participants 50 participants 38 participants 3 participants 39 participants
1.93  (7.6) 1.40  (7.8) 0.89  (6.8) 1.08  (6.0) -3.79  (7.3)
FACT-Hep Number Analyzed 30 participants 51 participants 38 participants 3 participants 39 participants
2.04  (1.53) 1.50  (17.5) 0.58  (18.2) -0.50  (6.5) -8.54  (17.0)
TOI Number Analyzed 30 participants 51 participants 38 participants 3 participants 39 participants
1.34  (13.3) 1.14  (14.6) 1.17  (12.2) -1.92  (7.7) -8.28  (13.7)
12.Secondary Outcome
Title Time to Worsening (TTW) of Symptoms (FACT-Hep)
Hide Description Time to worsening of symptoms used minimally important differences to evaluate Physical Well Being (PWB), Functional Well Being (FWB), Hepatocellular Cancer Symptoms (HCS), National Comprehensive Cancer Network (NCCN)/FACT Hepatocellular Symptoms (FHS), Trial-Outcome Index (TOI). PWB time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; FWB time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; HCS time to worsening was defined as participants who had change in a subscale of ≥ 5 point decrease from baseline; FHS time to worsening was defined as participants who had change in a subscale of ≥ 2 point decrease from baseline; TOI time to Worsening was defined as participants who had change in the subscale of ≥ 7 point decrease from baseline.
Time Frame Baseline to the worsening of symptoms (up to 567 days)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who completed a baseline and one post-baseline FACT-Hep TTW questionnaire. Due to low enrollment in Part C Cohort 1 - 160 mg reporting group, time-to-event analysis for TTW was not conducted for this subgroup. Per protocol, Part D collected safety data only.
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 2 - 300mg LY2157299
Hide Arm/Group Description:
80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle).
Overall Number of Participants Analyzed 30 61 37 40
Median (95% Confidence Interval)
Unit of Measure: Days
PWB
114.0 [1] 
(30.0 to NA)
113.0 [1] 
(57.0 to NA)
113.0
(58.0 to 170.0)
30.0
(29.0 to 57.0)
FWB
57.0
(30.0 to 86.0)
88.0
(57.0 to 371.0)
64.0
(30.0 to 172.0)
30.0
(29.0 to 58.0)
HCS
114.0 [1] 
(57.0 to NA)
113.0 [1] 
(85.0 to NA)
170.0
(57.0 to 567.0)
31.0
(29.0 to 57.0)
FHS
55.0
(29.0 to 86.0)
57.0
(30.0 to 113.0)
57.0
(30.0 to 113.0)
30.0
(29.0 to 30.0)
TOI
114.0 [1] 
(57.0 to NA)
113.0
(58.0 to 371.0)
179.0
(57.0 to 567.0)
30.0
(29.0 to 31.0)
[1]
Upper value of CI was non estimable
Time Frame Baseline up to 41.5 months
Adverse Event Reporting Description All participants who received at least one dose of study drug. Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
 
Arm/Group Title Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
Hide Arm/Group Description 80 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). 80 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). 150 mg LY2157299 given orally BID on days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). 80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle). 150 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle).
All-Cause Mortality
Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   33/37 (89.19%)      63/72 (87.50%)      26/40 (65.00%)      3/3 (100.00%)      36/44 (81.82%)      2/3 (66.67%)      5/5 (100.00%)    
Hide Serious Adverse Events
Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/37 (40.54%)      36/72 (50.00%)      16/40 (40.00%)      3/3 (100.00%)      28/44 (63.64%)      1/3 (33.33%)      2/5 (40.00%)    
Blood and lymphatic system disorders               
Anaemia  1  2/37 (5.41%)  2 7/72 (9.72%)  16 3/40 (7.50%)  5 1/3 (33.33%)  2 6/44 (13.64%)  9 0/3 (0.00%)  0 0/5 (0.00%)  0
Neutropenia  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Thrombocytopenia  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Cardiac disorders               
Acute coronary syndrome  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Acute myocardial infarction  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Angina unstable  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Atrial fibrillation  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Atrial thrombosis  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Cardiac failure  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Left ventricular dysfunction  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Left ventricular failure  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Gastrointestinal disorders               
Abdominal distension  1  0/37 (0.00%)  0 1/72 (1.39%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Abdominal pain  1  0/37 (0.00%)  0 3/72 (4.17%)  3 1/40 (2.50%)  1 0/3 (0.00%)  0 1/44 (2.27%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Abdominal pain upper  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Ascites  1  2/37 (5.41%)  2 4/72 (5.56%)  6 1/40 (2.50%)  1 0/3 (0.00%)  0 2/44 (4.55%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Diarrhoea  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Duodenal ulcer  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Gastric ulcer  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Gastric varices haemorrhage  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  2 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Gastrointestinal haemorrhage  1  0/37 (0.00%)  0 1/72 (1.39%)  2 1/40 (2.50%)  1 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1
Haematemesis  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Intestinal obstruction  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Intra-abdominal haemorrhage  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Large intestinal haemorrhage  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Lower gastrointestinal haemorrhage  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Melaena  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Nausea  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Oesophageal varices haemorrhage  1  1/37 (2.70%)  1 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Pancreatitis  1  1/37 (2.70%)  1 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Peritoneal haematoma  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Peritoneal haemorrhage  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Rectal haemorrhage  1  0/37 (0.00%)  0 1/72 (1.39%)  3 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Small intestinal haemorrhage  1  0/37 (0.00%)  0 1/72 (1.39%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Subileus  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Upper gastrointestinal haemorrhage  1  0/37 (0.00%)  0 1/72 (1.39%)  1 2/40 (5.00%)  4 1/3 (33.33%)  1 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Varices oesophageal  1  0/37 (0.00%)  0 1/72 (1.39%)  1 2/40 (5.00%)  3 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Vomiting  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
General disorders               
Asthenia  1  1/37 (2.70%)  1 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Chest discomfort  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
General physical health deterioration  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Pain  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Pyrexia  1  1/37 (2.70%)  1 2/72 (2.78%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Hepatobiliary disorders               
Acute hepatic failure  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1
Gallbladder rupture  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Hepatic failure  1  1/37 (2.70%)  1 2/72 (2.78%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Hepatic haematoma  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Hepatic haemorrhage  1  1/37 (2.70%)  1 2/72 (2.78%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Hepatic pain  1  0/37 (0.00%)  0 2/72 (2.78%)  2 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Hepatorenal syndrome  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Hyperbilirubinaemia  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Jaundice cholestatic  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Portal vein thrombosis  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Infections and infestations               
Anal abscess  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Arthritis bacterial  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Cellulitis  1  1/37 (2.70%)  1 0/72 (0.00%)  0 1/40 (2.50%)  2 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Diverticulitis  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Endocarditis  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Liver abscess  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 2/44 (4.55%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Lower respiratory tract infection  1  1/37 (2.70%)  1 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Lung infection  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Osteomyelitis  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Peritonitis bacterial  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Pneumonia  1  0/37 (0.00%)  0 4/72 (5.56%)  4 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Sepsis  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 2/44 (4.55%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Urinary tract infection  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Wound infection  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Injury, poisoning and procedural complications               
Cervical vertebral fracture  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Concussion  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Exposure during pregnancy  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Femur fracture  1  1/37 (2.70%)  1 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Pelvic fracture  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Post procedural haemorrhage  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Radiation pneumonitis  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Shunt stenosis  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Toxicity to various agents  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Investigations               
Blood bilirubin increased  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Liver function test abnormal  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Metabolism and nutrition disorders               
Decreased appetite  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Dehydration  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Fluid retention  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Hyperammonaemia  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Hyperglycaemia  1  1/37 (2.70%)  1 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Back pain  1  0/37 (0.00%)  0 2/72 (2.78%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Chondrocalcinosis pyrophosphate  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Joint effusion  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Musculoskeletal pain  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Myalgia  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Osteoarthritis  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Malignant ascites  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Malignant neoplasm progression  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Neoplasm progression  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Pancreatic neuroendocrine tumour  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1
Second primary malignancy  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Squamous cell carcinoma  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Squamous cell carcinoma of lung  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Squamous cell carcinoma of skin  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Tumour haemorrhage  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Tumour pain  1  2/37 (5.41%)  3 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Nervous system disorders               
Cerebrovascular accident  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Embolic stroke  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 1/3 (33.33%)  1 0/5 (0.00%)  0
Encephalopathy  1  1/37 (2.70%)  1 2/72 (2.78%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Haemorrhage intracranial  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Hepatic encephalopathy  1  2/37 (5.41%)  3 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1
Loss of consciousness  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Presyncope  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Transient ischaemic attack  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Psychiatric disorders               
Confusional state  1  1/37 (2.70%)  2 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Disorientation  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Renal and urinary disorders               
Acute kidney injury  1  1/37 (2.70%)  1 2/72 (2.78%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Haematuria  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Prerenal failure  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Renal disorder  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Renal impairment  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Renal injury  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Urinary retention  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Dyspnoea  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  3 0/3 (0.00%)  0 2/44 (4.55%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Pleural effusion  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Pneumonia aspiration  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Pneumonitis  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Pulmonary embolism  1  1/37 (2.70%)  1 0/72 (0.00%)  0 2/40 (5.00%)  2 1/3 (33.33%)  1 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Pulmonary infarction  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Pulmonary oedema  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Respiratory failure  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Skin and subcutaneous tissue disorders               
Drug eruption  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Vascular disorders               
Dry gangrene  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Shock haemorrhagic  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Thrombosis  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A Cohort 1 - 160 mg LY2157299 Part A Cohort 2 - 300 mg LY2157299 Part B - 300 mg LY2157299 Part C Cohort 1 - 160 mg LY2157299 + Sorafenib Part C Cohort 2 - 300 mg LY2157299 + Sorafenib Part D Cohort 1 - 160 mg LY2157299 + Ramucirumab Part D Cohort 2 - 300 mg LY2157299 + Ramucirumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/37 (86.49%)      64/72 (88.89%)      38/40 (95.00%)      3/3 (100.00%)      44/44 (100.00%)      3/3 (100.00%)      5/5 (100.00%)    
Blood and lymphatic system disorders               
Anaemia  1  9/37 (24.32%)  22 13/72 (18.06%)  23 10/40 (25.00%)  20 1/3 (33.33%)  4 12/44 (27.27%)  17 0/3 (0.00%)  0 0/5 (0.00%)  0
Neutropenia  1  3/37 (8.11%)  9 3/72 (4.17%)  4 1/40 (2.50%)  1 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Thrombocytopenia  1  2/37 (5.41%)  2 2/72 (2.78%)  2 3/40 (7.50%)  9 0/3 (0.00%)  0 7/44 (15.91%)  22 0/3 (0.00%)  0 0/5 (0.00%)  0
Ear and labyrinth disorders               
Tinnitus  1  0/37 (0.00%)  0 0/72 (0.00%)  0 3/40 (7.50%)  3 0/3 (0.00%)  0 2/44 (4.55%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Vertigo  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  1 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Gastrointestinal disorders               
Abdominal distension  1  2/37 (5.41%)  3 2/72 (2.78%)  2 5/40 (12.50%)  5 0/3 (0.00%)  0 4/44 (9.09%)  4 1/3 (33.33%)  1 2/5 (40.00%)  2
Abdominal pain  1  7/37 (18.92%)  7 11/72 (15.28%)  12 8/40 (20.00%)  10 1/3 (33.33%)  1 7/44 (15.91%)  8 0/3 (0.00%)  0 2/5 (40.00%)  2
Abdominal pain upper  1  1/37 (2.70%)  1 7/72 (9.72%)  10 4/40 (10.00%)  4 0/3 (0.00%)  0 4/44 (9.09%)  5 0/3 (0.00%)  0 1/5 (20.00%)  1
Ascites  1  5/37 (13.51%)  7 8/72 (11.11%)  8 2/40 (5.00%)  3 0/3 (0.00%)  0 6/44 (13.64%)  8 0/3 (0.00%)  0 0/5 (0.00%)  0
Barrett's oesophagus  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Constipation  1  5/37 (13.51%)  6 11/72 (15.28%)  14 7/40 (17.50%)  7 0/3 (0.00%)  0 6/44 (13.64%)  8 0/3 (0.00%)  0 1/5 (20.00%)  1
Diarrhoea  1  5/37 (13.51%)  8 10/72 (13.89%)  13 11/40 (27.50%)  15 1/3 (33.33%)  2 21/44 (47.73%)  43 1/3 (33.33%)  1 1/5 (20.00%)  1
Dry mouth  1  1/37 (2.70%)  1 4/72 (5.56%)  4 2/40 (5.00%)  2 1/3 (33.33%)  1 2/44 (4.55%)  2 1/3 (33.33%)  1 0/5 (0.00%)  0
Flatulence  1  2/37 (5.41%)  3 0/72 (0.00%)  0 1/40 (2.50%)  1 2/3 (66.67%)  2 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Gingival bleeding  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Nausea  1  6/37 (16.22%)  11 15/72 (20.83%)  21 9/40 (22.50%)  9 1/3 (33.33%)  2 12/44 (27.27%)  17 1/3 (33.33%)  1 1/5 (20.00%)  1
Portal hypertensive gastropathy  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Stomatitis  1  1/37 (2.70%)  1 3/72 (4.17%)  3 0/40 (0.00%)  0 0/3 (0.00%)  0 5/44 (11.36%)  8 0/3 (0.00%)  0 0/5 (0.00%)  0
Varices oesophageal  1  0/37 (0.00%)  0 2/72 (2.78%)  2 1/40 (2.50%)  1 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Vomiting  1  6/37 (16.22%)  6 12/72 (16.67%)  17 6/40 (15.00%)  11 1/3 (33.33%)  1 5/44 (11.36%)  11 0/3 (0.00%)  0 0/5 (0.00%)  0
General disorders               
Asthenia  1  5/37 (13.51%)  6 6/72 (8.33%)  6 4/40 (10.00%)  8 0/3 (0.00%)  0 6/44 (13.64%)  14 0/3 (0.00%)  0 0/5 (0.00%)  0
Chills  1  3/37 (8.11%)  3 2/72 (2.78%)  3 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 1/5 (20.00%)  1
Fatigue  1  9/37 (24.32%)  10 14/72 (19.44%)  17 14/40 (35.00%)  15 2/3 (66.67%)  2 11/44 (25.00%)  16 0/3 (0.00%)  0 2/5 (40.00%)  4
Influenza like illness  1  1/37 (2.70%)  1 1/72 (1.39%)  1 4/40 (10.00%)  4 0/3 (0.00%)  0 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Localised oedema  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Non-cardiac chest pain  1  0/37 (0.00%)  0 2/72 (2.78%)  2 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1
Oedema peripheral  1  5/37 (13.51%)  6 14/72 (19.44%)  16 12/40 (30.00%)  17 0/3 (0.00%)  0 10/44 (22.73%)  12 1/3 (33.33%)  1 1/5 (20.00%)  1
Pain  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1
Pyrexia  1  2/37 (5.41%)  4 6/72 (8.33%)  8 2/40 (5.00%)  2 1/3 (33.33%)  1 5/44 (11.36%)  13 0/3 (0.00%)  0 1/5 (20.00%)  1
Hepatobiliary disorders               
Hyperbilirubinaemia  1  3/37 (8.11%)  5 3/72 (4.17%)  3 1/40 (2.50%)  1 0/3 (0.00%)  0 4/44 (9.09%)  5 0/3 (0.00%)  0 0/5 (0.00%)  0
Portal vein thrombosis  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1
Infections and infestations               
Bronchitis  1  0/37 (0.00%)  0 3/72 (4.17%)  3 4/40 (10.00%)  4 0/3 (0.00%)  0 2/44 (4.55%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Furuncle  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Lung infection  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 0/3 (0.00%)  0 3/44 (6.82%)  7 0/3 (0.00%)  0 0/5 (0.00%)  0
Post abortion infection  1  0/5 (0.00%)  0 0/13 (0.00%)  0 0/4 (0.00%)  0 0/0  0 1/5 (20.00%)  1 0/0  0 0/0  0
Upper respiratory tract infection  1  1/37 (2.70%)  1 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 2/44 (4.55%)  3 1/3 (33.33%)  1 0/5 (0.00%)  0
Urinary tract infection  1  0/37 (0.00%)  0 2/72 (2.78%)  2 1/40 (2.50%)  2 1/3 (33.33%)  1 5/44 (11.36%)  5 0/3 (0.00%)  0 0/5 (0.00%)  0
Vaginal infection  1  0/5 (0.00%)  0 0/13 (0.00%)  0 0/4 (0.00%)  0 0/0  0 1/5 (20.00%)  1 0/0  0 0/0  0
Viral infection  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 1/3 (33.33%)  1 0/5 (0.00%)  0
Vulvovaginal candidiasis  1  0/5 (0.00%)  0 0/13 (0.00%)  0 0/4 (0.00%)  0 0/0  0 1/5 (20.00%)  1 0/0  0 0/0  0
Injury, poisoning and procedural complications               
Fall  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Investigations               
Aspartate aminotransferase increased  1  2/37 (5.41%)  3 3/72 (4.17%)  3 2/40 (5.00%)  2 1/3 (33.33%)  1 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Blood alkaline phosphatase increased  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  1 1/3 (33.33%)  1 2/44 (4.55%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Blood bilirubin increased  1  1/37 (2.70%)  1 3/72 (4.17%)  3 2/40 (5.00%)  2 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 1/5 (20.00%)  1
Haemoglobin decreased  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Weight decreased  1  4/37 (10.81%)  5 8/72 (11.11%)  8 10/40 (25.00%)  17 3/3 (100.00%)  7 24/44 (54.55%)  58 0/3 (0.00%)  0 0/5 (0.00%)  0
Weight increased  1  1/37 (2.70%)  1 7/72 (9.72%)  8 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Metabolism and nutrition disorders               
Decreased appetite  1  6/37 (16.22%)  7 7/72 (9.72%)  8 7/40 (17.50%)  7 2/3 (66.67%)  2 10/44 (22.73%)  15 0/3 (0.00%)  0 0/5 (0.00%)  0
Hypercalcaemia  1  3/37 (8.11%)  4 1/72 (1.39%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Hypoalbuminaemia  1  0/37 (0.00%)  0 3/72 (4.17%)  4 2/40 (5.00%)  3 0/3 (0.00%)  0 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Hypokalaemia  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 4/44 (9.09%)  6 0/3 (0.00%)  0 0/5 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Arthralgia  1  3/37 (8.11%)  5 3/72 (4.17%)  3 5/40 (12.50%)  5 0/3 (0.00%)  0 6/44 (13.64%)  6 0/3 (0.00%)  0 0/5 (0.00%)  0
Back pain  1  2/37 (5.41%)  3 5/72 (6.94%)  9 1/40 (2.50%)  2 0/3 (0.00%)  0 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Muscle spasms  1  2/37 (5.41%)  2 2/72 (2.78%)  3 5/40 (12.50%)  7 0/3 (0.00%)  0 6/44 (13.64%)  7 0/3 (0.00%)  0 0/5 (0.00%)  0
Muscular weakness  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 1/3 (33.33%)  1 0/5 (0.00%)  0
Musculoskeletal chest pain  1  0/37 (0.00%)  0 2/72 (2.78%)  3 1/40 (2.50%)  1 0/3 (0.00%)  0 1/44 (2.27%)  1 2/3 (66.67%)  2 0/5 (0.00%)  0
Myalgia  1  1/37 (2.70%)  1 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 10/44 (22.73%)  11 0/3 (0.00%)  0 0/5 (0.00%)  0
Pain in extremity  1  1/37 (2.70%)  1 3/72 (4.17%)  3 1/40 (2.50%)  2 0/3 (0.00%)  0 3/44 (6.82%)  6 0/3 (0.00%)  0 0/5 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Basal cell carcinoma  1  0/37 (0.00%)  0 0/72 (0.00%)  0 1/40 (2.50%)  1 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Malignant ascites  1  1/37 (2.70%)  1 5/72 (6.94%)  5 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Tumour pain  1  4/37 (10.81%)  4 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Nervous system disorders               
Embolic stroke  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 1/3 (33.33%)  1 0/5 (0.00%)  0
Headache  1  1/37 (2.70%)  1 4/72 (5.56%)  4 5/40 (12.50%)  5 0/3 (0.00%)  0 3/44 (6.82%)  3 0/3 (0.00%)  0 1/5 (20.00%)  1
Hepatic encephalopathy  1  2/37 (5.41%)  2 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Peripheral sensory neuropathy  1  3/37 (8.11%)  3 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Somnolence  1  2/37 (5.41%)  2 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Taste disorder  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 1/5 (20.00%)  1
Psychiatric disorders               
Anxiety  1  1/37 (2.70%)  1 4/72 (5.56%)  4 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Confusional state  1  2/37 (5.41%)  2 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1
Insomnia  1  2/37 (5.41%)  2 5/72 (6.94%)  6 4/40 (10.00%)  4 0/3 (0.00%)  0 5/44 (11.36%)  5 0/3 (0.00%)  0 0/5 (0.00%)  0
Renal and urinary disorders               
Haematuria  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Nocturia  1  0/37 (0.00%)  0 2/72 (2.78%)  2 0/40 (0.00%)  0 0/3 (0.00%)  0 0/44 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1
Reproductive system and breast disorders               
Erectile dysfunction  1  1/32 (3.13%)  1 0/59 (0.00%)  0 0/36 (0.00%)  0 0/3 (0.00%)  0 2/39 (5.13%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Cough  1  3/37 (8.11%)  3 5/72 (6.94%)  5 3/40 (7.50%)  4 0/3 (0.00%)  0 3/44 (6.82%)  4 0/3 (0.00%)  0 1/5 (20.00%)  1
Dyspnoea  1  3/37 (8.11%)  3 9/72 (12.50%)  10 6/40 (15.00%)  7 0/3 (0.00%)  0 5/44 (11.36%)  5 1/3 (33.33%)  1 1/5 (20.00%)  2
Epistaxis  1  1/37 (2.70%)  3 2/72 (2.78%)  2 3/40 (7.50%)  3 0/3 (0.00%)  0 4/44 (9.09%)  5 3/3 (100.00%)  3 1/5 (20.00%)  1
Oropharyngeal pain  1  1/37 (2.70%)  1 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 1/44 (2.27%)  1 0/3 (0.00%)  0 1/5 (20.00%)  1
Skin and subcutaneous tissue disorders               
Alopecia  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 0/3 (0.00%)  0 9/44 (20.45%)  9 0/3 (0.00%)  0 0/5 (0.00%)  0
Dry skin  1  1/37 (2.70%)  1 3/72 (4.17%)  3 1/40 (2.50%)  1 0/3 (0.00%)  0 7/44 (15.91%)  7 0/3 (0.00%)  0 0/5 (0.00%)  0
Erythema multiforme  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  1 1/3 (33.33%)  1 1/44 (2.27%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0
Night sweats  1  2/37 (5.41%)  2 0/72 (0.00%)  0 0/40 (0.00%)  0 1/3 (33.33%)  1 0/44 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  1 1/3 (33.33%)  3 28/44 (63.64%)  61 0/3 (0.00%)  0 0/5 (0.00%)  0
Pruritus  1  7/37 (18.92%)  9 9/72 (12.50%)  10 8/40 (20.00%)  10 1/3 (33.33%)  1 12/44 (27.27%)  16 0/3 (0.00%)  0 0/5 (0.00%)  0
Rash  1  0/37 (0.00%)  0 1/72 (1.39%)  1 0/40 (0.00%)  0 1/3 (33.33%)  3 10/44 (22.73%)  11 0/3 (0.00%)  0 0/5 (0.00%)  0
Rash maculo-papular  1  3/37 (8.11%)  3 1/72 (1.39%)  1 2/40 (5.00%)  2 1/3 (33.33%)  1 1/44 (2.27%)  2 0/3 (0.00%)  0 0/5 (0.00%)  0
Skin exfoliation  1  0/37 (0.00%)  0 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Skin lesion  1  1/37 (2.70%)  1 0/72 (0.00%)  0 0/40 (0.00%)  0 0/3 (0.00%)  0 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Vascular disorders               
Flushing  1  0/37 (0.00%)  0 2/72 (2.78%)  3 0/40 (0.00%)  0 0/3 (0.00%)  0 3/44 (6.82%)  3 0/3 (0.00%)  0 0/5 (0.00%)  0
Haematoma  1  0/37 (0.00%)  0 1/72 (1.39%)  1 1/40 (2.50%)  1 0/3 (0.00%)  0 4/44 (9.09%)  4 0/3 (0.00%)  0 0/5 (0.00%)  0
Hypertension  1  0/37 (0.00%)  0 1/72 (1.39%)  1 2/40 (5.00%)  2 0/3 (0.00%)  0 8/44 (18.18%)  10 0/3 (0.00%)  0 0/5 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment

Per the protocol, following an interim analysis, the decision was taken to no longer randomize participants to the 160 mg LY2157299 arm.

Per protocol, Part D collected safety data only.

Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
EMail: ClinicalTrials.gov@lilly.com
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01246986    
Other Study ID Numbers: 13665
H9H-MC-JBAK ( Other Identifier: Eli Lilly and Company )
2010-022338-10 ( EudraCT Number )
First Submitted: November 1, 2010
First Posted: November 24, 2010
Results First Submitted: June 4, 2020
Results First Posted: August 7, 2020
Last Update Posted: January 12, 2021