Trial Outcomes & Findings for Phase 2 Study of Gemcitabine or Gemcitabine + Enzastaurin in Participants With Advanced or Metastatic Pancreatic Cancer (NCT NCT00267020)

NCT ID: NCT00267020

Last Updated: 2020-08-31

Results Overview

OS was the duration from randomization to death. OS was censored at the last contact for participants who were alive, at the cut-off date.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 130 participants
• Primary outcome timeframe: Randomization to the date of death from any cause up to 27.7 months
• Results posted on: 2020-08-31

Participant Flow

Participant flow reports those participants who discontinued from study drug.

Participant milestones

Measure	Enzastaurin+Gemcitabine Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Overall Study STARTED	86	44
Overall Study Received at Least 1 Dose	82	39
Overall Study Per-Protocol Population	81	38
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	86	43

Reasons for withdrawal

Measure	Enzastaurin+Gemcitabine Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Overall Study Adverse Event	22	5
Overall Study Death	2	1
Overall Study Withdrawal by Subject	17	7
Overall Study Physician Decision	3	2
Overall Study Disease Progression	39	25
Overall Study Unrelated Complication	1	1
Overall Study Sponsor Request	1	0
Overall Study Other	1	2

Baseline Characteristics

Phase 2 Study of Gemcitabine or Gemcitabine + Enzastaurin in Participants With Advanced or Metastatic Pancreatic Cancer

Baseline characteristics by cohort

Measure	Enzastaurin+Gemcitabine n=86 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=44 Participants Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Total n=130 Participants Total of all reporting groups
Age, Continuous	68.3 years n=5 Participants	64.1 years n=7 Participants	67.6 years n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	12 Participants n=7 Participants	52 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	32 Participants n=7 Participants	78 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=5 Participants	41 Participants n=7 Participants	118 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	69 Participants n=5 Participants	35 Participants n=7 Participants	104 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	86 Participants n=5 Participants	44 Participants n=7 Participants	130 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - Fully Active	36 Participants n=5 Participants	16 Participants n=7 Participants	52 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 - Ambulatory, Restricted Strenuous Activity	43 Participants n=5 Participants	25 Participants n=7 Participants	68 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 - Ambulatory, No Work Activities	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Body Surface Area (BSA)	1.8 square meter (m^2) STANDARD_DEVIATION 0.24 • n=5 Participants	1.9 square meter (m^2) STANDARD_DEVIATION 0.21 • n=7 Participants	1.8 square meter (m^2) STANDARD_DEVIATION 0.23 • n=5 Participants
Diagnosis Stage Stage IIA	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Diagnosis Stage Stage IIB	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Diagnosis Stage Stage III	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Diagnosis Stage Stage IV	72 Participants n=5 Participants	35 Participants n=7 Participants	107 Participants n=5 Participants
Current Stage Stage IIB	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Current Stage Stage III	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Current Stage Stage IV	78 Participants n=5 Participants	38 Participants n=7 Participants	116 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to the date of death from any cause up to 27.7 months

Population: Intent-to -treat (ITT) population: All randomized participants. Participants censored: Enzastaurin+Gemcitabine = 17; Gemcitabine = 11.

OS was the duration from randomization to death. OS was censored at the last contact for participants who were alive, at the cut-off date.

Outcome measures

Measure	Enzastaurin+Gemcitabine n=86 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=44 Participants Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Overall Survival (OS)	5.6 months Interval 4.2 to 6.9	5.1 months Interval 3.6 to 8.1

SECONDARY outcome

Timeframe: Randomization to measured progressive disease (PD) up to 19.9 months

Population: Per Protocol Population: Randomized participants who had: 1) histological or cytological diagnosis of locally advanced (Stage II, III) or metastatic (Stage IV) adenocarcinoma of the pancreas; 2) no concurrent systemic chemotherapy; 3) presence of measurable disease at baseline; and 4) received at least 1 dose of study drug.

Response rate was defined as percentage of responders (best study response recorded as CR or PR) from the qualified number of participants for tumor response analysis. Response defined using Response Evaluation Criteria In Solid Tumors (RECIST, v1.0) criteria: CR was disappearance of all target lesions for at least 4 weeks. PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.

Percentage of participants was calculated as: (The number of responders with CR or PR/ The number of participants qualified for tumor response analysis) × 100.

Outcome measures

Measure	Enzastaurin+Gemcitabine n=81 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=38 Participants Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) CR	1.2 percentage of participants Interval 0.0 to 6.7	0 percentage of participants Interval 0.0 to 0.0
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) PR	7.4 percentage of participants Interval 2.8 to 15.4	5.3 percentage of participants Interval 0.6 to 17.7

SECONDARY outcome

Timeframe: Randomization to measured PD or death from any cause up to 21.6 months

Population: Intent-to-treat (ITT) population: All randomized participants. Participants censored: Enzastaurin+Gemcitabine = 21; Gemcitabine = 10.

PFS was defined as the time from the date of randomization to the first date of documented progressive disease (PD) or death due to any cause, whichever occurred first. PFS was censored at the date of the last assessment visit for participants who were still alive at data cut-off and who had not had documented progressive disease. Participants who started a new treatment before progression were censored as of the date of the start of new treatment.

Outcome measures

Measure	Enzastaurin+Gemcitabine n=86 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=44 Participants Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Progression Free Survival (PFS)	3.4 months Interval 2.4 to 4.0	3.0 months Interval 1.9 to 4.5

SECONDARY outcome

Timeframe: Time of response to PD or death from any cause up to 19.9 months

Population: Participants in the Per Protocol population with a CR or PR: With histological or cytological diagnosis of locally advanced adenocarcinoma of the pancreas; no concurrent systemic chemotherapy; presence of measurable disease at baseline; and treatment with at least 1 dose of study drug. Censored: Enzastaurin+Gemcitabine = 1; Gemcitabine = 0.

The duration of a complete response (CR) or partial response (PR) was defined, using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, as the time from first objective status assessment of CR or PR to the first time of disease progression or death as a result of any cause. Using the Response Evaluation Criteria in Solid Tumors (RECIST V1.0) criteria, CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD. Duration of response was censored at the date of the last assessment visit for responders who were still alive at data cut-off and had no documented progressive disease (PD).

Outcome measures

Measure	Enzastaurin+Gemcitabine n=7 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=2 Participants Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Duration of Response	4.6 months Interval 3.7 to 13.9	9.2 months Interval 5.6 to 12.9

SECONDARY outcome

Timeframe: Baseline through end of study up to 27.7 months

Population: All randomized participants who received at least one dose of study drug and had data for FACT-Hep questionnaire.

FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72. The Trial Outcomes Index (TOI) is the sum of the PWB, FWB and Hep subscales with a scores range of 0 to 128. The Total FACT-Hep score was the sum of all questions with a scores range of 0 to 180. The Total FACT-G score was the sum of the 27 questions in the PWB, SFWB, EWB and FWB with a scores range of 0 to 108. The FACT-Hep Symptoms Index with 8 key questions and scores range of 0 to 32 from the Hep Subscale. Higher score in sub-score or total score indicates better QOL and better health state. Participants were classified as "Improved" if they had positive change from baseline, "Worsened" if they had negative change from baseline, and "Stable" otherwise.

Outcome measures

Measure	Enzastaurin+Gemcitabine n=33 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=17 Participants Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Total FACT-Hep score- Improved	30.0 units on a scale Standard Deviation 16.81	27.5 units on a scale Standard Deviation 17.91
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Physical well-being- Improved	7.2 units on a scale Standard Deviation 3.48	6.5 units on a scale Standard Deviation 2.71
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Physical well-being- Stable	0.3 units on a scale Standard Deviation 1.16	0.8 units on a scale Standard Deviation 1.80
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Physical well-being- Worsened	-10.0 units on a scale Standard Deviation 4.08	-7.8 units on a scale Standard Deviation 3.96
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Social well-being- Improved	3.8 units on a scale Standard Deviation 0.64	4.7 units on a scale Standard Deviation 2.10
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Social well-being- Stable	0.1 units on a scale Standard Deviation 1.06	-0.6 units on a scale Standard Deviation 1.21
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Social well-being- Worsened	-6.5 units on a scale Standard Deviation 3.80	-5.5 units on a scale Standard Deviation 2.66
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Emotional well-being- Improved	6.9 units on a scale Standard Deviation 4.76	6.7 units on a scale Standard Deviation 3.79
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Emotional well-being- Stable	0 units on a scale Standard Deviation 1.29	-0.1 units on a scale Standard Deviation 1.36
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Emotional well-being- Worsened	-5.8 units on a scale Standard Deviation 2.57	-8.2 units on a scale Standard Deviation 4.15
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Functional well-being- Improved	6.8 units on a scale Standard Deviation 3.63	6.5 units on a scale Standard Deviation 1.73
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Functional well-being- Stable	-0.2 units on a scale Standard Deviation 1.40	-1.1 units on a scale Standard Deviation 0.90
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Functional well-being- Worsened	-10.6 units on a scale Standard Deviation 5.37	-8.5 units on a scale Standard Deviation 4.42
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Hepatobiliary cancer subscale- Improved	12.7 units on a scale Standard Deviation 4.67	12.0 units on a scale Standard Deviation 5.20
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Hepatobiliary cancer subscale- Stable	0.5 units on a scale Standard Deviation 3.00	0.7 units on a scale Standard Deviation 3.78
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Hepatobiliary cancer subscale- Worsened	-14.6 units on a scale Standard Deviation 4.70	-10.0 units on a scale Standard Deviation 4.32
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Total Outcome Index- Improved	21.4 units on a scale Standard Deviation 11.20	19.0 units on a scale Standard Deviation 11.49
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Total outcome index- Stable	-1.6 units on a scale Standard Deviation 5.40	-1.3 units on a scale Standard Deviation 4.76
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Total outcome index- Worsened	-35.9 units on a scale Standard Deviation 13.03	-23.0 units on a scale Standard Deviation 9.88
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Total FACT-Hep score- Stable	-1.2 units on a scale Standard Deviation 5.65	0 units on a scale Standard Deviation 4.19
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Total FACT-Hep score- Worsened	-37.9 units on a scale Standard Deviation 13.71	-26.6 units on a scale Standard Deviation 12.26
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Total FACT-G-score- Improved	19.1 units on a scale Standard Deviation 11.63	24.1 units on a scale Standard Deviation 18.95
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Total FACT-G-score- Stable	-0.5 units on a scale Standard Deviation 3.56	-0.6 units on a scale Standard Deviation 4.17
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) Total FACT-G-score- Worsened	-20.1 units on a scale Standard Deviation 10.59	-21.2 units on a scale Standard Deviation 10.75
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) FACT Hep Symptoms Index- Improved	7.4 units on a scale Standard Deviation 3.95	6.3 units on a scale Standard Deviation 2.50
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) FACT Hep Symptoms Index- Stable	0.5 units on a scale Standard Deviation 1.45	0.1 units on a scale Standard Deviation 1.85
Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL)) FACT Hep Symptoms Index- Worsened	-7.0 units on a scale Standard Deviation 3.31	-7.0 units on a scale Standard Deviation 2.16

SECONDARY outcome

Timeframe: Randomization to date of death from any cause up to 27.7 months

Population: All participants who received at least 1 dose of study drug. Participants censored: Below median = 4; Above median =4.

OS was the duration from randomization to death from any cause. For participants who were alive at data cut-off, OS was censored at the last contact. Participants were categorized into 2 groups based on their steady state drug levels of Enzastaurin (total analyte=enzastaurin + LSN326020 [metabolite]): those participants below the median and those participants above the median [2786.042 nanomoles per /liter (nmol/l)]. The steady state drug levels and clinical outcomes were not evaluated for the Gemcitabine only treatment group.

Outcome measures

Measure	Enzastaurin+Gemcitabine n=57 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Relationship of Steady-State Drug Levels to Clinical Outcomes of Overall Survival (OS) Below median	7.2 months Interval 5.1 to 10.6	—
Relationship of Steady-State Drug Levels to Clinical Outcomes of Overall Survival (OS) Above median	5.6 months Interval 3.2 to 6.9	—

SECONDARY outcome

Timeframe: Beginning of treatment up to 27.7 months

Population: Randomized participants who had: 1) Histological or cytological diagnosis of locally advanced (Stage II, III) or metastatic (Stage IV) adenocarcinoma of the pancreas; 2) no concurrent systemic chemotherapy; 3) presence of measurable disease at baseline; and 4) received at least 1 dose of study drug and had data for overall response.

The overall disease control rate was calculated as percent of participants with overall response of complete response (CR), partial response (PR) or stable disease (SD) over number of per-protocol population. Using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, CR: disappearance of all target and non-target lesions; PR: as at least a 30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD) was defined as at least 20% increase in sum of LD of target lesions; SD: small changes that did not meet above criteria.

Participants were categorized into 2 groups based on their steady state drug levels of Enzastaurin (total analyte=enzastaurin + LSN326020 [metabolite]): participants below the median and participants above the median [2754.521 nanomoles per liter (nmol/l)].

The steady state drug levels and clinical outcomes were not evaluated for the Gemcitabine only group.

Outcome measures

Measure	Enzastaurin+Gemcitabine n=28 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) CR (Below median)	3.6 percentage of participants Interval 0.1 to 18.3	—
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) CR (Above median)	0.0 percentage of participants Interval 0.0 to 0.0	—
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) PR (Below median)	17.9 percentage of participants Interval 6.1 to 36.9	—
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) PR (Above median)	3.6 percentage of participants Interval 0.1 to 18.3	—
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) SD (Below median)	57.1 percentage of participants Interval 37.2 to 75.5	—
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) SD (Above median)	39.3 percentage of participants Interval 21.5 to 59.4	—
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) PD (Below median)	14.3 percentage of participants Interval 4.0 to 32.7	—
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) PD (Above median)	32.1 percentage of participants Interval 15.9 to 52.4	—
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) Disease Control (Below median)	78.6 percentage of participants Interval 59.0 to 91.7	—
Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control) Disease Control (Above median)	42.9 percentage of participants Interval 24.5 to 62.8	—

SECONDARY outcome

Timeframe: Cycles 1 to 6, and post-treatment (up to 27.7 months)

Population: Safety population: All randomized participants who received at least 1 dose of study drug.

CA19-9 is a tumor biomarker which was measured in the blood to assess the effect of treatment with enzastaurin.

Outcome measures

Measure	Enzastaurin+Gemcitabine n=82 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=39 Participants Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Carbohydrate Antigen 19-9 (CA 19-9) Concentration in the Blood Cycle 1	31708.5 kilo units/liter (kU/L) Standard Deviation 134178.00	12038.6 kilo units/liter (kU/L) Standard Deviation 26659.50
Carbohydrate Antigen 19-9 (CA 19-9) Concentration in the Blood Cycle 2	12828.4 kilo units/liter (kU/L) Standard Deviation 33051.54	40764.9 kilo units/liter (kU/L) Standard Deviation 143995.67
Carbohydrate Antigen 19-9 (CA 19-9) Concentration in the Blood Cycle 3	24709.5 kilo units/liter (kU/L) Standard Deviation 114098.20	1573.0 kilo units/liter (kU/L) Standard Deviation 2811.74
Carbohydrate Antigen 19-9 (CA 19-9) Concentration in the Blood Cycle 4	37261.0 kilo units/liter (kU/L) Standard Deviation 168939.81	1102.7 kilo units/liter (kU/L) Standard Deviation 1547.67
Carbohydrate Antigen 19-9 (CA 19-9) Concentration in the Blood Cycle 5	392.3 kilo units/liter (kU/L) Standard Deviation 744.91	403.1 kilo units/liter (kU/L) Standard Deviation 541.91
Carbohydrate Antigen 19-9 (CA 19-9) Concentration in the Blood Cycle 6	600.9 kilo units/liter (kU/L) Standard Deviation 1268.90	938.5 kilo units/liter (kU/L) Standard Deviation 1542.34
Carbohydrate Antigen 19-9 (CA 19-9) Concentration in the Blood Post-treatment 1st visit	19420.5 kilo units/liter (kU/L) Standard Deviation 45867.95	11351.3 kilo units/liter (kU/L) Standard Deviation 23890.66
Carbohydrate Antigen 19-9 (CA 19-9) Concentration in the Blood Post-treatment 2nd visit	19557.7 kilo units/liter (kU/L) Standard Deviation 32615.58	93955.9 kilo units/liter (kU/L) Standard Deviation 176684.42

SECONDARY outcome

Timeframe: Baseline through study completion (Up To 27.7 Months)

Population: Safety population: All participants who received at least 1 dose of study drug.

Clinically significant events were defined as SAEs and other non-serious adverse events (AEs). Participants who died due to progressive disease (PD), AEs while on treatment or died during the 30 day post-treatment are included. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Measure	Enzastaurin+Gemcitabine n=82 Participants Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=39 Participants Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.
Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) (Toxicity) Non-serious AEs	80 Participants	38 Participants
Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) (Toxicity) SAEs	49 Participants	23 Participants
Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) (Toxicity) Deaths due to PD	3 Participants	1 Participants
Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) (Toxicity) Deaths due to AEs	4 Participants	1 Participants
Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) (Toxicity) Deaths within 30-days after treatment	3 Participants	1 Participants

Adverse Events

Enzastaurin+Gemcitabine

Serious events: 49 serious events

Other events: 80 other events

Deaths: 0 deaths

Gemcitabine

Serious events: 23 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Enzastaurin+Gemcitabine n=82 participants at risk Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=39 participants at risk Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each of each 28-day cycle.
Nervous system disorders Thrombotic stroke	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Intestinal obstruction	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Intestinal perforation	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Blood and lymphatic system disorders Anaemia	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Blood and lymphatic system disorders Thrombocytopenia	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Cardiac disorders Acute myocardial infarction	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Cardiac disorders Atrial fibrillation	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Cardiac disorders Atrial flutter	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Cardiac disorders Cardiac arrest	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Cardiac disorders Myocardial infarction	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Abdominal pain	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Abdominal pain upper	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Ascites	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Constipation	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Diarrhoea	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Ileus	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Nausea	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Oesophageal varices haemorrhage	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Pancreatitis	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Pancreatitis acute	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Small intestinal obstruction	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Vomiting	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Asthenia	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Chest pain	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Disease progression	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Gait disturbance	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Oedema peripheral	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Pain	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Thrombosis in device	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Hepatobiliary disorders Bile duct obstruction	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Hepatobiliary disorders Cholangitis	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Hepatobiliary disorders Hyperbilirubinaemia	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Hepatobiliary disorders Jaundice	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Bacteraemia	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Bacterial sepsis	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Cellulitis	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Device related infection	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Escherichia sepsis	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Infection	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Peritonitis	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Pneumonia	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Sepsis	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Urinary tract infection	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Urosepsis	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Blood bilirubin increased	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Weight decreased	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Decreased appetite	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Dehydration	8.5% 7/82 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Failure to thrive	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Hyperglycaemia	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Cerebrovascular accident	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Dizziness	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Encephalopathy	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Syncope	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Psychiatric disorders Confusional state	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Psychiatric disorders Depression	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Psychiatric disorders Hallucination	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Renal and urinary disorders Renal failure	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Renal and urinary disorders Renal failure acute	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Hydropneumothorax	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	8.5% 7/82 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Surgical and medical procedures Internal fixation of fracture	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Vascular disorders Arteriosclerosis	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Vascular disorders Deep vein thrombosis	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	12.8% 5/39 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Vascular disorders Venous thrombosis	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.

Other adverse events

Measure	Enzastaurin+Gemcitabine n=82 participants at risk Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later. Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.	Gemcitabine n=39 participants at risk Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each of each 28-day cycle.
Blood and lymphatic system disorders Leukopenia	31.7% 26/82 • Number of events 26 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	35.9% 14/39 • Number of events 14 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Blood and lymphatic system disorders Lymphopenia	3.7% 3/82 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Eye disorders Vision blurred	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Abdominal distension	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Abdominal pain	31.7% 26/82 • Number of events 26 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	20.5% 8/39 • Number of events 9 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Ascites	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Constipation	29.3% 24/82 • Number of events 24 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	28.2% 11/39 • Number of events 11 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Diarrhoea	30.5% 25/82 • Number of events 25 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	25.6% 10/39 • Number of events 10 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Dyspepsia	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Gastrointestinal haemorrhage	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Haemorrhoids	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Nausea	42.7% 35/82 • Number of events 35 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	33.3% 13/39 • Number of events 13 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Oesophagitis	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Gastrointestinal disorders Vomiting	20.7% 17/82 • Number of events 17 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	17.9% 7/39 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Chills	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Fatigue	61.0% 50/82 • Number of events 50 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	56.4% 22/39 • Number of events 22 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Oedema	12.2% 10/82 • Number of events 10 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Oedema peripheral	30.5% 25/82 • Number of events 25 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	30.8% 12/39 • Number of events 12 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Pain	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
General disorders Pyrexia	18.3% 15/82 • Number of events 15 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	15.4% 6/39 • Number of events 6 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Hepatobiliary disorders Hyperbilirubinaemia	8.5% 7/82 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Immune system disorders Hypersensitivity	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Pneumonia	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Infections and infestations Skin infection	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Injury, poisoning and procedural complications Vascular access complication	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Alanine aminotransferase increased	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	17.9% 7/39 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Aspartate aminotransferase increased	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	15.4% 6/39 • Number of events 6 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Blood alkaline phosphatase increased	12.2% 10/82 • Number of events 10 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	15.4% 6/39 • Number of events 6 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Blood creatinine increased	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Haemoglobin decreased	56.1% 46/82 • Number of events 46 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	59.0% 23/39 • Number of events 23 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Laboratory test abnormal	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Neutrophil count decreased	39.0% 32/82 • Number of events 32 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	46.2% 18/39 • Number of events 18 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Platelet count decreased	56.1% 46/82 • Number of events 46 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	51.3% 20/39 • Number of events 20 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Weight decreased	11.0% 9/82 • Number of events 9 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	15.4% 6/39 • Number of events 6 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Investigations Weight increased	3.7% 3/82 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Decreased appetite	28.0% 23/82 • Number of events 23 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	41.0% 16/39 • Number of events 16 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Dehydration	11.0% 9/82 • Number of events 9 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Hyperglycaemia	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	12.8% 5/39 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Hyperkalaemia	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	0.00% 0/39 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Hypoalbuminaemia	8.5% 7/82 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	10.3% 4/39 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Hypocalcaemia	3.7% 3/82 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Hypokalaemia	8.5% 7/82 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	10.3% 4/39 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Metabolism and nutrition disorders Hyponatraemia	11.0% 9/82 • Number of events 9 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Musculoskeletal and connective tissue disorders Back pain	11.0% 9/82 • Number of events 10 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	12.8% 5/39 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Musculoskeletal and connective tissue disorders Bone pain	3.7% 3/82 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Musculoskeletal and connective tissue disorders Muscular weakness	12.2% 10/82 • Number of events 10 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	23.1% 9/39 • Number of events 9 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Musculoskeletal and connective tissue disorders Myalgia	3.7% 3/82 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Musculoskeletal and connective tissue disorders Pain in extremity	7.3% 6/82 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	10.3% 4/39 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Ataxia	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Dizziness	12.2% 10/82 • Number of events 10 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	10.3% 4/39 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Dysgeusia	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Headache	7.3% 6/82 • Number of events 6 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Peripheral sensory neuropathy	7.3% 6/82 • Number of events 6 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Speech disorder	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Nervous system disorders Tremor	0.00% 0/82 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Psychiatric disorders Anxiety	7.3% 6/82 • Number of events 6 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Psychiatric disorders Depressed mood	9.8% 8/82 • Number of events 8 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Psychiatric disorders Insomnia	14.6% 12/82 • Number of events 12 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Renal and urinary disorders Chromaturia	12.2% 10/82 • Number of events 10 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Dyspnoea	20.7% 17/82 • Number of events 17 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	17.9% 7/39 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.4% 2/82 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Hiccups	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.1% 5/82 • Number of events 5 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	2.6% 1/39 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Skin and subcutaneous tissue disorders Pruritus	3.7% 3/82 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Skin and subcutaneous tissue disorders Rash erythematous	4.9% 4/82 • Number of events 4 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Vascular disorders Haematoma	7.3% 6/82 • Number of events 6 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Vascular disorders Hypertension	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Vascular disorders Hypotension	8.5% 7/82 • Number of events 7 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	7.7% 3/39 • Number of events 3 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.
Vascular disorders Thrombosis	1.2% 1/82 • Number of events 1 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.	5.1% 2/39 • Number of events 2 • Baseline through study completion (27.7 months) Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60