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Trial record 18 of 42 for:    Malignant Hyperthermia 5

A Study of LY2334737 in Participants With Cancer That is Advanced and/or Has Spread

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ClinicalTrials.gov Identifier: NCT01648764
Recruitment Status : Completed
First Posted : July 24, 2012
Results First Posted : June 17, 2019
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Malignant Solid Tumor
Solid Tumor
Metastatic Tumor
Intervention Drug: LY2334737
Enrollment 73
Recruitment Details  
Pre-assignment Details Participant Flow is reporting discontinuation from study drug. Completed participants were all those who completed Cycle 1.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
Hide Arm/Group Description 40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Period Title: Overall Study
Started 3 3 3 3 3 5 9 3 3 7 3 9 7 12
Received at Least 1 Dose of Study Drug 3 3 3 3 3 5 9 3 3 7 3 9 7 12
Completed 3 2 3 3 3 3 4 3 3 4 3 4 3 9
Not Completed 0 1 0 0 0 2 5 0 0 3 0 5 4 3
Reason Not Completed
Progressive Disease             0             1             0             0             0             1             1             0             0             2             0             1             2             1
Adverse Event             0             0             0             0             0             1             0             0             0             1             0             3             1             1
Death             0             0             0             0             0             0             1             0             0             0             0             0             0             1
Withdrawal by Subject             0             0             0             0             0             0             2             0             0             0             0             0             1             0
Investigator Decision             0             0             0             0             0             0             1             0             0             0             0             1             0             0
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY2334737 - Arm A Dose Confirmation Total
Hide Arm/Group Description 40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28 -ay treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. Total of all reporting groups
Overall Number of Baseline Participants 3 3 3 3 3 5 9 3 3 7 3 9 7 12 73
Hide Baseline Analysis Population Description
All enrolled participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 9 participants 3 participants 3 participants 7 participants 3 participants 9 participants 7 participants 12 participants 73 participants
57.7  (3.8) 60.0  (20.3) 56.3  (11.2) 49.7  (17.2) 49.7  (9.6) 68.2  (6.2) 54.4  (11.1) 55.7  (7.2) 65.0  (5.0) 60.1  (9.3) 52.7  (20.0) 66.0  (4.6) 61.9  (9.8) 63.0  (6.4) 59.9  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 9 participants 3 participants 3 participants 7 participants 3 participants 9 participants 7 participants 12 participants 73 participants
Female
1
  33.3%
0
   0.0%
1
  33.3%
1
  33.3%
0
   0.0%
2
  40.0%
3
  33.3%
1
  33.3%
0
   0.0%
1
  14.3%
1
  33.3%
6
  66.7%
4
  57.1%
4
  33.3%
25
  34.2%
Male
2
  66.7%
3
 100.0%
2
  66.7%
2
  66.7%
3
 100.0%
3
  60.0%
6
  66.7%
2
  66.7%
3
 100.0%
6
  85.7%
2
  66.7%
3
  33.3%
3
  42.9%
8
  66.7%
48
  65.8%
Race  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 9 participants 3 participants 3 participants 7 participants 3 participants 9 participants 7 participants 12 participants 73 participants
Caucasian
3
 100.0%
2
  66.7%
1
  33.3%
3
 100.0%
3
 100.0%
5
 100.0%
8
  88.9%
3
 100.0%
2
  66.7%
7
 100.0%
2
  66.7%
9
 100.0%
7
 100.0%
11
  91.7%
66
  90.4%
African
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   4.1%
West Asian
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
Hispanic
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
1
   8.3%
3
   4.1%
Eastern Cooperative Oncology Group (ECOG)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 9 participants 3 participants 3 participants 7 participants 3 participants 9 participants 7 participants 12 participants 73 participants
0 3 2 3 3 1 3 4 2 3 4 1 5 2 7 43
1 0 1 0 0 2 2 5 1 0 3 2 3 5 5 29
2 0 0 0 0 0 0 0 0 0 0 0 1 0 0 1
[1]
Measure Description: ECOG Performance Status: 0=asymptomatic, fully active, can carry on all predisease performance without restrictions; 1=symptomatic, fully ambulatory, but restricted in physically strenuous activity, able to perform light/sedentary tasks; 2=symptomatic, ambulatory, capable of all self-care but unable to carry out work activities, up and about more than 50% of waking hours and in bed less than 50% of day.
Disease Stage   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 9 participants 3 participants 3 participants 7 participants 3 participants 9 participants 7 participants 12 participants 73 participants
Stage III 0 0 1 0 0 1 0 0 0 1 0 0 0 3 6
Stage IV 3 3 2 3 3 4 9 3 3 6 3 9 7 9 67
[1]
Measure Description: Stage III –the cancer has spread to nearby tissue or spread to far away lymph nodes. Stage IV –the cancer has spread to other organs of the body such as the other lung, brain or liver.
Country of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 3 participants 3 participants 5 participants 9 participants 3 participants 3 participants 7 participants 3 participants 9 participants 7 participants 12 participants 73 participants
France
3
 100.0%
3
 100.0%
3
 100.0%
2
  66.7%
1
  33.3%
2
  40.0%
5
  55.6%
2
  66.7%
3
 100.0%
4
  57.1%
2
  66.7%
4
  44.4%
1
  14.3%
6
  50.0%
41
  56.2%
Germany
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
2
  66.7%
3
  60.0%
3
  33.3%
1
  33.3%
0
   0.0%
2
  28.6%
0
   0.0%
4
  44.4%
3
  42.9%
2
  16.7%
21
  28.8%
United States
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
1
  14.3%
1
  33.3%
1
  11.1%
3
  42.9%
4
  33.3%
11
  15.1%
1.Primary Outcome
Title Recommended Dose for Phase 2 Studies
Hide Description Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). The MTD was the highest dose level at which <2 out of 6 participants experienced a dose-limiting toxicity (DLT) in Cycle 1. DLT was an adverse event (AE) during Cycle 1 that was likely related to LY2334737 and fulfilled any of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 nonhematological (except nausea/vomiting controlled with treatment); Grade 3 neutropenia with fever or any Grade 4 neutropenia with or without fever; Grade 3 thrombocytopenia with ≥Grade 2 bleeding or Grade 4 thrombocytopenia with or without bleeding; A recovery period longer than 14 days from last dose of LY2334737 to values allowing Cycle 2 to start; Other significant drug-related toxicity deemed by investigator to be dose limiting or that caused the participant to withdraw from the study. Pharmacokinetics and pharmacodynamics (PK/PD) were also taken into consideration for Phase 2 recommended dose.
Time Frame Baseline up to 28 days postdose in Cycle 1 (28-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug during dose escalation and dose confirmation treatment arms.
Arm/Group Title LY2334737
Hide Arm/Group Description:
LY2334737 was administered as 2 Arms A and B. Participants in treatment Arm A were administered LY2334737 orally in escalating doses of 40 to 100 milligrams (mg) of LY2334737 every other day for 21 days followed by 7 days without study drug. Participants in treatment Arm B were administered LY2334737 orally in escalating doses of 40 to 90 mg every day for 7 days followed by 7 days without study drug and then repeated. Both treatment cycles were 28 days.
Overall Number of Participants Analyzed 73
Measure Type: Number
Unit of Measure: mg every other day for 21 days
90
2.Secondary Outcome
Title Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for LY2334737
Hide Description AUC over the dosing interval (AUC0-Ƭ) of LY2334737 for Arm A (single dose) is 0 to 48 hours postdose. AUC0-Ƭ of LY2334737 for Arm B (multiple doses) is 0 to 24 hours postdose and AUC time 0 to infinity (AUC0-∞) for LY2334737.
Time Frame Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had AUC0-Ƭ and AUC0-∞ values.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation and Dose Confirmation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation
Hide Arm/Group Description:
40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 3 2 3 3 3 14 8 3 3 7 2 7 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hours per milliliter (ng*h/mL)
C1 D1 AUC0-Ƭ Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 14 participants 8 participants 3 participants 3 participants 7 participants 2 participants 7 participants 7 participants
188
(4%)
315
(34%)
250
(45%)
225
(32%)
279
(33%)
469
(58%)
429
(14%)
133
(70%)
154
(14%)
312
(27%)
437
(89%)
232
(54%)
455
(35%)
C1 D1 AUC0-∞ Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 14 participants 8 participants 3 participants 3 participants 7 participants 2 participants 7 participants 7 participants
188
(4%)
315
(34%)
250
(45%)
225
(32%)
279
(33%)
469
(58%)
429
(14%)
134
(71%)
156
(15%)
314
(27%)
440
(89%)
234
(54%)
460
(35%)
C1 D21, AUC0-Ƭ Number Analyzed 3 participants 2 participants 3 participants 2 participants 3 participants 13 participants 3 participants 3 participants 3 participants 5 participants 2 participants 5 participants 3 participants
219
(31%)
364
(2%)
188
(76%)
318
(22%)
341
(76%)
525
(93%)
647
(47%)
227
(72%)
233
(12%)
445
(20%)
620
(119%)
392
(31%)
580
(31%)
3.Secondary Outcome
Title Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for 2’2’-Difluorodeoxycytidine (dFdC)
Hide Description AUC over the dosing interval (AUC0-Ƭ) of dFdC (a metabolite of LY2334737) for Arm A (following a single dose of LY2334737) AUC0-Ƭ is 0-48 hours postdose, Arm B (following multiple doses of LY2334737) AUC 0-Ƭ is 0-24 hours postdose and AUC from time 0 to infinity (AUC0-∞).
Time Frame Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours post dose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours post dose of 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had AUC 0-Ƭ and AUC 0-∞ values.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation and Dose Confirmation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation
Hide Arm/Group Description:
40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 3 2 3 3 3 14 7 3 3 7 2 7 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hours/milliliter (ng*h/mL)
C1 D1 AUC 0-Ƭ Number Analyzed 1 participants 0 participants 3 participants 3 participants 3 participants 14 participants 7 participants 3 participants 3 participants 7 participants 1 participants 7 participants 7 participants
12.1 [1] 
(NA%)
30.8
(54%)
30.7
(13%)
25.4
(45%)
54.9
(65%)
59.4
(14%)
21.2
(108%)
19.3
(25%)
27.2
(15%)
52.1 [1] 
(NA%)
24.9
(46%)
46.0
(28%)
C1 D1 AUC 0-∞ Number Analyzed 1 participants 0 participants 3 participants 3 participants 3 participants 14 participants 7 participants 3 participants 3 participants 7 participants 1 participants 7 participants 7 participants
12.1 [2] 
(NA%)
30.7
(54%)
30.7
(14%)
25.3
(46%)
54.8
(65%)
59.1
(15%)
21.1
(109%)
19.2
(24%)
27.2
(15%)
54.7 [1] 
(NA%)
25.4
(46%)
46.4
(27%)
C1 D21 AUC 0-Ƭ Number Analyzed 3 participants 2 participants 1 participants 2 participants 1 participants 13 participants 3 participants 1 participants 3 participants 5 participants 1 participants 5 participants 1 participants
12.5
(30%)
26.6
(30%)
31.1 [3] 
(NA%)
35.7
(18%)
53.4 [3] 
(NA%)
59.6
(90%)
55.6
(67%)
38.6 [3] 
(NA%)
27.8
(37%)
28.9
(8%)
74.8 [3] 
(NA%)
45.5
(102%)
119 [3] 
(NA%)
[1]
Result is for 1 participant only.
[2]
Results is for 1 participant only
[3]
Results is for 1 participant only.
4.Secondary Outcome
Title Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) for Difluorodeoxyuridine (dFdU)
Hide Description Daily AUC from time 0 to 24 hours (AUC 0-24) of dFdU (a metabolite of LY2334737) for Arm A (single dose of LY2334737) and Arm B (multiple doses of LY2334737).
Time Frame Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had AUC0-24 dFdU results.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation and Dose Confirmation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation
Hide Arm/Group Description:
40 milligram (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 3 2 3 3 3 14 8 3 3 7 3 7 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hours per milliliter (ng*h/mL)
C1 D1 Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 14 participants 8 participants 3 participants 3 participants 7 participants 2 participants 7 participants 7 participants
4990
(3%)
7250
(20%)
8060
(48%)
10800
(23%)
9350
(30%)
11500
(35%)
10800
(37%)
6080
(16%)
7020
(6%)
8660
(16%)
9620
(3%)
9370
(39%)
12400
(11%)
C1 D 21 Number Analyzed 3 participants 2 participants 3 participants 2 participants 3 participants 13 participants 3 participants 3 participants 3 participants 5 participants 2 participants 5 participants 3 participants
22300
(31%)
21500
(49%)
24800
(18%)
26100
(4%)
21200
(57%)
28300
(38%)
29800
(23%)
29300
(37%)
32200
(2%)
35700
(37%)
37100
(27%)
35600
(27%)
39900
(35%)
5.Secondary Outcome
Title Pharmacokinetics: Maximum Plasma Concentration (Cmax)
Hide Description Cmax for LY2334737 and its metabolites 2’2’-difluorodeoxycytidine (dFdC) and difluorodeoxyuridine (dFdU).
Time Frame Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had Cmax values.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation and Dose Confirmation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation
Hide Arm/Group Description:
40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 3 2 3 3 3 14 8 3 3 7 2 7 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
C1 D1-LY2334737 Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 14 participants 8 participants 3 participants 3 participants 7 participants 2 participants 7 participants 7 participants
53.9
(40%)
62.6
(79%)
72.4
(75%)
91.8
(96%)
118
(92%)
171
(105%)
89.3
(72%)
46.5
(33%)
79.4
(8%)
112
(37%)
134
(192%)
55.1
(51%)
163
(44%)
C1 D21-LY2334737 Number Analyzed 3 participants 2 participants 3 participants 2 participants 3 participants 13 participants 3 participants 3 participants 3 participants 5 participants 2 participants 5 participants 3 participants
68.4
(11%)
110
(41%)
35.7
(165%)
93.1
(43%)
61.5
(473%)
126
(71%)
147
(26%)
48.8
(102%)
37.9
(118%)
106
(42%)
108
(51%)
74.4
(46%)
137
(62%)
C1 D1-dFdC Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 14 participants 7 participants 3 participants 3 participants 7 participants 2 participants 7 participants 7 participants
3.39
(35%)
4.83
(60%)
6.55
(109%)
13.0
(27%)
10.4
(72%)
16.0
(77%)
12.1
(91%)
10.9
(19%)
10.6
(26%)
11.2
(29%)
9.35
(69%)
6.14
(60%)
16.0
(43%)
C1 D21-dFdC Number Analyzed 3 participants 2 participants 3 participants 2 participants 2 participants 13 participants 3 participants 3 participants 3 participants 5 participants 2 participants 5 participants 3 participants
3.64
(19%)
8.22
(4%)
3.94
(180%)
11.3
(33%)
10.9
(243%)
10.2
(80%)
10.9
(76%)
5.81
(131%)
4.05
(64%)
6.99
(39%)
7.03
(17%)
6.93
(46%)
16.7
(125%)
C1 D1-dFdU Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 14 participants 8 participants 3 participants 3 participants 7 participants 2 participants 7 participants 7 participants
262
(6%)
393
(24%)
419
(42%)
532
(27%)
467
(23%)
594
(29%)
564
(27%)
305
(14%)
369
(13%)
442
(24%)
485
(10%)
466
(37%)
620
(11%)
C1 D21-dFdU Number Analyzed 3 participants 2 participants 3 participants 2 participants 3 participants 13 participants 3 participants 3 participants 3 participants 5 participants 2 participants 5 participants 3 participants
1060
(25%)
992
(51%)
1120
(18%)
1330
(20%)
1050
(52%)
1390
(35%)
1360
(19%)
1450
(38%)
1670
(6%)
1650
(32%)
1690
(29%)
1680
(26%)
1940
(28%)
6.Secondary Outcome
Title Number of Participants With Best Overall Response (BOR)
Hide Description Response defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. Complete Response defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Partial Response defined as ≥30% decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD) defined as ≥20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions, or appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease was defined as small changes that did not meet above criteria and unknown defined as response status was not known. The BOR was the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started).
Time Frame Baseline to measured disease progression up to 33 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
Hide Arm/Group Description:
40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 3 3 3 3 3 5 9 3 3 7 3 9 7 12
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Partial Response 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Stable Disease 1 2 2 0 1 0 1 0 1 2 1 0 0 0
Progressive Disease 2 1 1 3 2 2 4 3 2 3 2 3 4 10
Unknown 0 0 0 0 0 3 4 0 0 2 0 6 3 2
7.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description

PFS was defined as the time from date of first dose to the first observation of disease progression or death due to any cause.

Due to the different tumor types, schedules and doses, the PFS was not analyzed.

Time Frame Baseline to measured disease progression or death up to 33 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants analyzed. No data collected for PFS.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
Hide Arm/Group Description:
40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 0 0 0 0 0 0 0 0 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Percentage of Participants With Changes in QT Interval (>30 Milliseconds) From Baseline
Hide Description Fridericia-corrected QT (QTcF) interval corrected for heart rate was assessed using triplicate 12-lead electrocardiograms (ECGs). Change in QT interval from baseline was calculated using a time matched approach, that is change from baseline was calculated by subtracting the respective reading taken at the same nominal time on Day-1 from the reading taken on Days 1 and 21; change from baseline was calculated by subtracting the last non-missing ECG assessment on or prior to Day 1, 0.5 hours prior to dose from assessment on Day 2 and Day 22. The outlying QTcF intervals were defined using the criteria: change from baseline in mean QTcF interval >30 milliseconds
Time Frame Day -1: 24.5 hours, 22 hours and 17 hours predose; Cycle 1 Days 1 and 21, 0.5 hours predose, 2 hours, 7 hours and 24 hours postdose (28-day cycles)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
Hide Arm/Group Description:
40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 3 3 3 3 3 5 9 3 3 7 3 9 7 12
Measure Type: Number
Unit of Measure: percentage of participants
33.3 33.3 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 11.1 0.0 0.0
9.Secondary Outcome
Title Percentage of Participants With Changes in R-R Interval From Baseline
Hide Description Changes in R-R interval from baseline was calculated using a time matched approach, that is change from baseline was calculated by subtracting the respective reading taken at the same nominal time on Day -1 from the reading taken on Days 1 and 21; change from baseline was calculated by subtracting the last non-missing electrocardiogram (ECG) assessment on or prior to Day 1 and 0.5 hours prior to dose for Day 2 and Day 22. Percentage of participants with changes in R-R interval from baseline was calculated as the number of participants with a change not equal to 0 across all time points divided by the number of treated participants multiplied by 100.
Time Frame Day -1: 24.5 hours, 22 hours and 17 hours predose; Cycle 1 Days 1 and 21: 0.5 hours predose, 2 hours, 7 hours and 24 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug with R-R interval data at all time points.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
Hide Arm/Group Description:
40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 3 3 3 3 3 5 9 3 3 7 3 9 7 12
Measure Type: Number
Unit of Measure: percentage of participants
100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0
10.Secondary Outcome
Title Pharmacokinetics: Minimum Plasma Concentration (Cmin)
Hide Description Cmin for LY2334737 and its metabolite 2’2’-difluorodeoxycytidine (dFdC).
Time Frame Cycle 1 Day 1 (C1 D1): 0.5, 1.5, 2, 3.5, 7, 24 hours postdose; Cycle 1 Day 21 (C1 D21): predose, 0.5, 2, 3 to 4, 7, 24 hours postdose of 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and had Cmin values
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation and Dose Confirmation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation
Hide Arm/Group Description:
40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 3 2 3 3 3 14 8 3 3 7 2 7 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
C1 D1 LY Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 14 participants 8 participants 3 participants 3 participants 7 participants 2 participants 7 participants 7 participants
0.451
(129%)
0.319
(10%)
0.458
(43%)
0.279
(66%)
0.392
(15%)
0.901
(94%)
0.920
(45%)
0.379
(118%)
0.279
(98%)
0.456
(36%)
0.773
(57%)
0.665
(80%)
0.898
(84%)
C1 D21 LY Number Analyzed 3 participants 2 participants 3 participants 2 participants 3 participants 13 participants 3 participants 3 participants 3 participants 5 participants 2 participants 5 participants 3 participants
0.264
(34%)
0.223
(89%)
0.519
(1479%)
1.01
(59%)
0.568
(18%)
1.04
(146%)
0.934
(274%)
0.347
(148%)
0.523
(43%)
1.50
(66%)
0.347
(251%)
1.04
(89%)
0.561
(395%)
C1 D1 dFdC Number Analyzed 3 participants 2 participants 3 participants 3 participants 3 participants 14 participants 7 participants 3 participants 3 participants 7 participants 2 participants 7 participants 7 participants
0.774
(52%)
1.89
(28%)
0.507
(47%)
0.891
(45%)
0.918
(56%)
0.901
(108%)
0.928
(179%)
1.45
(49%)
0.567
(53%)
1.10
(60%)
0.840
(133%)
0.809
(99%)
1.65
(134%)
C1 D21 dFdC Number Analyzed 3 participants 2 participants 3 participants 2 participants 2 participants 13 participants 3 participants 3 participants 3 participants 5 participants 2 participants 5 participants 3 participants
0.431
(24%)
0.949
(47%)
1.25
(37%)
0.612
(198%)
1.87
(155%)
0.647
(107%)
0.643
(76%)
1.21
(170%)
0.409
(82%)
1.19
(112%)
0.804
(363%)
1.49
(80%)
2.96
(180%)
11.Other Pre-specified Outcome
Title Number of Participants With Dose-Limiting Toxicity (DLT)
Hide Description DLT was defined as an adverse event (AE) during Cycle 1 that was likely related to the LY2334737 and fulfilled any of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 nonhematological (except nausea/vomiting controlled with treatment); Grade 3 neutropenia with fever or any Grade 4 neutropenia with or without fever; Grade 3 thrombocytopenia with ≥ Grade 2 bleeding or Grade 4 thrombocytopenia; with or without bleeding A recovery period longer than 14 days from the last dose of LY2334737 to values allowing Cycle 2 to start; other significant drug-related toxicity deemed by the investigator to be dose limiting or that caused the participant to withdraw from the study.
Time Frame Cycle 1 (28-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
Hide Arm/Group Description:
40 milligrams (mg) LY2334737 (LY) administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
Overall Number of Participants Analyzed 3 3 3 3 3 5 9 3 3 7 3 9 7 12
Measure Type: Count of Participants
Unit of Measure: Participants
0 0 0 0 0 0 3 0 0 1 0 1 2 1
Time Frame [Not Specified]
Adverse Event Reporting Description Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug.
 
Arm/Group Title 40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
Hide Arm/Group Description 40 milligrams (mg) LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 50 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 60 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 70 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 80 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 100 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 40 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 50 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 60 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 70 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 80 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 90 mg LY2334737 administered orally every day for 7 days followed by 7 days without study drug then repeated (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met. 90 mg LY2334737 administered orally every other day for 21 days followed by 7 days without study drug (28-day treatment cycle). Participants could have received additional treatment cycles until discontinuation criterion was met.
All-Cause Mortality
40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
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 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   2/3 (66.67%)      1/3 (33.33%)      1/3 (33.33%)      1/3 (33.33%)      1/3 (33.33%)      5/5 (100.00%)      5/9 (55.56%)      1/3 (33.33%)      1/3 (33.33%)      2/7 (28.57%)      2/3 (66.67%)      5/9 (55.56%)      6/7 (85.71%)      6/12 (50.00%)    
Blood and lymphatic system disorders                             
Anaemia  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Gastrointestinal disorders                             
Abdominal pain  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0
Ascites  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Colonic obstruction  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Diarrhoea  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 1/7 (14.29%)  1 0/12 (0.00%)  0
Gastric haemorrhage  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Gastrointestinal haemorrhage  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Proctocolitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0
Rectal haemorrhage  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0
Vomiting  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  2 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0
General disorders                             
Asthenia  1  1/3 (33.33%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Disease progression  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
General physical health deterioration  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Mucosal inflammation  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0
Oedema peripheral  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Pyrexia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 1/7 (14.29%)  1 0/12 (0.00%)  0
Hepatobiliary disorders                             
Bile duct stenosis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Cholangitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Cholestasis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Hepatic function abnormal  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0
Hyperbilirubinaemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Immune system disorders                             
Cytokine release syndrome  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0
Infections and infestations                             
Infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Klebsiella bacteraemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Pneumonia  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/3 (33.33%)  1 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Urinary tract infection  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Investigations                             
Blood bilirubin increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Electrocardiogram qt prolonged  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Troponin t increased  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Metabolism and nutrition disorders                             
Decreased appetite  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Dehydration  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Musculoskeletal and connective tissue disorders                             
Arthralgia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Back pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Musculoskeletal chest pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                             
Tumour pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Nervous system disorders                             
Dizziness  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0
Psychiatric disorders                             
Anxiety  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Confusional state  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Renal and urinary disorders                             
Urinary retention  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/3 (33.33%)  1 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                             
Dyspnoea  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/5 (40.00%)  2 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Haemoptysis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Pulmonary embolism  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 1/12 (8.33%)  1
Surgical and medical procedures                             
Exeresis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Vascular disorders                             
Hypotension  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 0/12 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
40 mg LY - Arm A Dose Escalation 50 mg LY - Arm A Dose Escalation 60 mg LY - Arm A Dose Escalation 70 mg LY - Arm A Dose Escalation 80 mg LY - Arm A Dose Escalation 90 mg LY - Arm A Dose Escalation 100 mg LY - Arm A Dose Escalation 40 mg LY - Arm B Dose Escalation 50 mg LY - Arm B Dose Escalation 60 mg LY - Arm B Dose Escalation 70 mg LY - Arm B Dose Escalation 80 mg LY - Arm B Dose Escalation 90 mg LY - Arm B Dose Escalation 90 mg LY - Arm A Dose Confirmation
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 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   3/3 (100.00%)      3/3 (100.00%)      3/3 (100.00%)      3/3 (100.00%)      3/3 (100.00%)      5/5 (100.00%)      9/9 (100.00%)      3/3 (100.00%)      3/3 (100.00%)      7/7 (100.00%)      3/3 (100.00%)      9/9 (100.00%)      6/7 (85.71%)      12/12 (100.00%)    
Blood and lymphatic system disorders                             
Anaemia  1  3/3 (100.00%)  4 1/3 (33.33%)  1 2/3 (66.67%)  2 1/3 (33.33%)  1 0/3 (0.00%)  0 1/5 (20.00%)  1 0/9 (0.00%)  0 1/3 (33.33%)  1 2/3 (66.67%)  2 3/7 (42.86%)  3 3/3 (100.00%)  3 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Disseminated intravascular coagulation  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Lymphopenia  1  2/3 (66.67%)  3 3/3 (100.00%)  4 2/3 (66.67%)  3 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 1/3 (33.33%)  1 3/3 (100.00%)  4 1/7 (14.29%)  1 2/3 (66.67%)  2 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Neutropenia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/3 (33.33%)  2 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Thrombocytopenia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 1/3 (33.33%)  2 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Cardiac disorders                             
Tachycardia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Ear and labyrinth disorders                             
Hearing impaired  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Tinnitus  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Vertigo  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Eye disorders                             
Conjunctivitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/5 (20.00%)  1 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Eyelid oedema  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Gastrointestinal disorders                             
Abdominal discomfort  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Abdominal distension  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Abdominal pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 3/7 (42.86%)  3 1/3 (33.33%)  1 4/9 (44.44%)  4 1/7 (14.29%)  1 1/12 (8.33%)  1
Abdominal pain lower  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Abdominal pain upper  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 2/9 (22.22%)  2 0/7 (0.00%)  0 0/12 (0.00%)  0
Ascites  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Constipation  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 2/3 (66.67%)  2 1/5 (20.00%)  1 3/9 (33.33%)  3 1/3 (33.33%)  1 1/3 (33.33%)  1 0/7 (0.00%)  0 1/3 (33.33%)  1 3/9 (33.33%)  3 1/7 (14.29%)  1 1/12 (8.33%)  1
Diarrhoea  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 2/3 (66.67%)  2 0/3 (0.00%)  0 2/5 (40.00%)  2 3/9 (33.33%)  3 2/3 (66.67%)  3 0/3 (0.00%)  0 2/7 (28.57%)  2 0/3 (0.00%)  0 3/9 (33.33%)  3 2/7 (28.57%)  2 3/12 (25.00%)  3
Dry mouth  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/3 (33.33%)  1 2/9 (22.22%)  2 0/7 (0.00%)  0 0/12 (0.00%)  0
Dyspepsia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Flatulence  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Gastrointestinal disorder  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Gastrooesophageal reflux disease  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Haematochezia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 1/12 (8.33%)  1
Melaena  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Nausea  1  1/3 (33.33%)  3 2/3 (66.67%)  3 1/3 (33.33%)  1 2/3 (66.67%)  2 2/3 (66.67%)  2 4/5 (80.00%)  4 7/9 (77.78%)  8 1/3 (33.33%)  1 1/3 (33.33%)  1 2/7 (28.57%)  2 2/3 (66.67%)  5 3/9 (33.33%)  3 4/7 (57.14%)  4 6/12 (50.00%)  6
Obstruction gastric  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Oesophagitis  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Oral disorder  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Pancreatitis chronic  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Stomatitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 1/9 (11.11%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Subileus  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Vomiting  1  2/3 (66.67%)  3 2/3 (66.67%)  2 0/3 (0.00%)  0 1/3 (33.33%)  4 2/3 (66.67%)  2 5/5 (100.00%)  5 6/9 (66.67%)  7 2/3 (66.67%)  2 1/3 (33.33%)  1 1/7 (14.29%)  1 2/3 (66.67%)  3 4/9 (44.44%)  4 2/7 (28.57%)  2 3/12 (25.00%)  3
General disorders                             
Asthenia  1  2/3 (66.67%)  3 2/3 (66.67%)  2 3/3 (100.00%)  4 2/3 (66.67%)  2 1/3 (33.33%)  1 2/5 (40.00%)  2 4/9 (44.44%)  4 1/3 (33.33%)  1 1/3 (33.33%)  1 2/7 (28.57%)  2 1/3 (33.33%)  1 4/9 (44.44%)  4 1/7 (14.29%)  1 4/12 (33.33%)  4
Chest pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Chills  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 0/3 (0.00%)  0 0/5 (0.00%)  0 2/9 (22.22%)  2 1/3 (33.33%)  2 0/3 (0.00%)  0 2/7 (28.57%)  2 1/3 (33.33%)  1 3/9 (33.33%)  3 1/7 (14.29%)  1 3/12 (25.00%)  3
Condition aggravated  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Face oedema  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  2 0/7 (0.00%)  0 0/3 (0.00%)  0 0/9 (0.00%)  0 0/7 (0.00%)  0 0/12 (0.00%)  0
Fatigue  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 3/5 (60.00%)  3 4/9 (44.44%)  4 1/3 (33.33%)  1 0/3 (0.00%)  0 1/7 (14.29%)  2 1/3 (33.33%)  1 2/9 (22.22%)  2 1/7 (14.29%)  1 3/12 (25.00%)  3
General physical health deterioration  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0 1/9 (11.11%)  1 0/7 (0.00%)  0 0/12 (0.00%)  0
Influenza like illness  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 0/5 (0.00%)  0 0/9 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 1/9 (11.11%)  1 2/7 (28.57%)  2 3/12 (25.00%)  3
Mucosal inflammation  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 2/3 (66.67%)  2 0/3 (0.00%)  0 1/5 (20.00%)  1 2/9 (22.22%)  2 0/3 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0 0/9 (0.00%)  0 1/7 (14.29%)  1 3/12 (25.00%)  3
Multi-organ failure  1  0/3 (0.00%)  0 0/3 (0.00%)  0